Other Articles That May Interest YouThis is a reading syllabus posted on the American Thoracic Society website. Although this is not mandatory reading for yourselves (residents rotating through the Pulmonary rotation), you may find some of the articles of interest to help flesh out certain topics.

ARDS

Ashbaugh DG, Bigelow DB, Petty TL, et al. Acute respiratory distress in adults. Lancet 1967;2:319-323. Original description of ARDS and use of PEEP in treating ARDS. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=4143721

ARDS Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for ALI and ARDS. NEJM 2000;342:1301-8. Results of ARMA study are basis for low- stretch/low tidal volume ventilation strategy. http://content.nejm.org/cgi/content/abstract/342/18/1301

Eichacker PQ, Gerstenberger EP, Banks SM, et al. Meta-analysis of ALI and ARDS trials testing low tidal volumes. AJRCCM 2002;166:1510-14.  In this highly controversial analysis, the authors question the validity of the ARDS network study above, arguing that 1) the mortality benefit resulted from excess mortality in the traditional arm, 2) the traditional arm did not receive the standard of care (authors argue the traditional arm received excessively large tidal volumes), and 3) very low tidal volumes are harmful.  See links to commentary for rebuttals to all of these points. http://ajrccm.atsjournals.org/cgi/content/full/166/11/1510                

Weinert CR, Gross CR, Marinelli WA. Impact of randomized trial results on acute lung injury ventilator therapy in teaching hospitals. AJRCCM 2003;167:1304-9.  This study is interesting in light of the above two studies. It found the average tidal volume used at 2 non-ARDSnet teaching hospitals in the 5 years leading up to the release of results from ARDSnet was 11.2 ml/kg IBW (compared to 12 cc/kg IBW used in the ARDSnet traditional arm).  Tidal volumes were slowly declining around the time ARDSnet results were released, but were still 10.1ml/kg of IBW 2 years after their release.  Less than 1% of patients were receiving 6 cc/kg IBW or less. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12574072

Amato MBP, Barbas CSV, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in ARDS. NEJM 1998;338:347-54. Small, randomized, study famous for using a combination of the lower inflection point of the pressure-volume curve to set PEEP, recruitment maneuvers (CPAP 35-40 cm x 40 sec.), and low-tidal volumes (< 6cc/kg). 28-day mortality was lower in the intervention group, but the conventional group had an unusually high mortality (71%). Patients overall received higher PEEP than in the ARMA study. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9449727

Meduri GU, Headley AS, Golden E, et al. Effect of prolonged methyprednisolone therapy in unresolving ARDS. JAMA 1998;280:159-65. Encouraging results obtained in this small RCT of steroids vs. placebo in the later, fibrosing stage of ARDS (days 6-12 in this study) including improved mortality. However, some patients in the placebo group crossed over to the steroid group. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9669790

Rubenfeld GD, Caldwell E, Granton J, et al. Interobserver variability in applying a radiographic definition for ARDS. CHEST 1999;116:1347-53. A group of 21 experts in ARDS were asked to determine whether a series of CXRs met the American-European Consensus Conference radiographic criterion for ARDS. Interobserver agreement was only moderate. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10559098

Hudson LD, Milberg JA, Anardi D, Maunder RJ. Clinical risks for development of ARDS. AJRCCM 1995;151:293-301. Study describes the incidence of ARDS in patients with various clinical risk factors. Also found 1) greater mortality in at-risk patients that develop ARDS and 2) ARDS develops within 48 to 72 hours of the time clinical risk is identified in the vast majority of patients.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7842182

Davidson TA, Caldwell ES, Curtis JR, et al. Reduced quality of life in survivors of ARDS compared with critically ill control patients. JAMA 1999;281:354-60. One of the first studies to look at quality of life of ARDS survivors.  It found decreased quality of life related to severity and complications of ARDS, rather than duration of mechanical ventilation or hospital stay, compared to matched, critically-ill control patients.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9929089

**See also Invasive and Non-invasive Mechanical Ventilation

Asthma

Rowe BH, Bota GW, Fabris L, et al. Inhaled budesonide in discharge from the emergency department: a randomized controlled trial. JAMA 1999;281:2119-26. Study found the addition of inhaled steroid to oral steroid at the time of discharge from the emergency department reduced the rate of relapse by about half. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10367823

Haahtala T, Jarvinen M, Kava T, et al. Comparison of a beta-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma. NEJM 1991;325:388-92. This randomized, blinded comparison of the above two drugs was important in establishing inhaled corticosteroids as the first line treatment for asthma. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2062329

O'Driscoll BR, Kalra S, Wilson M, et al. Double-blind trial of steroid tapering in acute asthma. Lancet 1993;341:324-7. Study found tapering steroids after treatment with 10 days of steroids for an asthma exacerbation was unnecessary

as long as patient was on an inhaled corticosteroid. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8094111

Laviolette M, Malmstrom K, Lu S, et al. Montelukast added to inhaled beclomethasone in treatment of asthma. AJRCCM 1999;160:1862-68. This randomized, double-blinded study supports the addition of a leukotriene inhibitor for asthmatics with inadequate symptom control with inhaled corticosteroid alone. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10588598

Malmstrom K, Rodriguez-Gomez G, Guerra J, et al. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized controlled trial. Ann Intern Med 1999;130:487-95. Both inhaled steroid and a leukotriene inhibitor were better than placebo. Beclomethasone was significantly better than montelukast in reducing exacerbations and symptoms. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10075616

Lazarus SC, Boushey HA, Fahy JV et al. Long-acting beta2-agonist monotherapy vs. continued therapy with inhaled corticosteroids in patients with persistent asthma: a RCT. JAMA 2001;285:2583-93.  Switching from low dose ICS to longacting beta2-agonist in patients with well-controlled, persistent asthma increases the risk of treatment failure and asthma exacerbations.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11368732

Busse WW.  Anti-immunoglobulin E (omalizumab) therapy in allergic asthma.  Review summarizes several large RCT studying the role of anti-IgE antibody in allergic asthma.  The use of anti-IgE is associated with decreased frequency of exacerbations, reductions in corticosteroid dose, and improved quality of life in symptomatic patients with moderate to severe allergic asthma.   http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11704612

Edelman JM, Turpin JA, Bronsky EA, et al. Oral montelukast compared with inhaled salmeterol to prevent exercise- induced bronchoconstriction. A randomized, double-blind trial. Ann Intern Med 2000;132(2):97-104. Study found leukotriene blockade has equal efficacy to a beta-agonist for the prevention of EIB and that daily administration is not associated with a reduction in efficacy that is seen with daily dosing of long-acting beta agonists. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10644288

Suissa S, Blais L, Ernst P. Patterns of increasing beta-agonist use and the risk of fatal or near-fatal asthma. Eur Respir J 1994;7:1602-9. Nested case control study found increased and escalating use of beta-agonists were associated with an increased risk of death from asthma. Findings suggest poorly controlled asthma should not be managed with increased dosage of beta-agonists alone. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7995388

Lange P, Parner J, Vestbo J, Schnohr P, Jensen G. A 15-year follow-up study of ventilatory function in adults with asthma. N Engl J Med 1998;339:1194-200.

Noteworthy for being one of the studies showing that a portion of patients with asthma go on to develop fixed airway obstruction. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9780339

Web site for latest treatment guidelines:

http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm

**See also Invasive Mechanical Ventilation and Occupational Medicine

Community-acquired Pneumonia

Skerrett SJ. Diagnostic testing for CAP. Clin Chest Med 1999;20:531-48. Covers the techniques and yield of non-invasive and invasive diagnostic tests as well as the laboratory diagnosis of specific infections. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10516902

Niederman MS, Mandell LA, Anzueto A, et al. Guidelines for the management of adults with community-acquired pneumonia: diagnosis, assessment of severity, antimicrobial therapy, and prevention. AJRCCM 2001;163:1730-54. Latest recommendations from the ATS. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11401897

Bartlett JG, Dowell SF, Mandell LA, et al. Practice guidelines for the management of community- acquired pneumonia in adults. (From the IDSA). Clin Infect Dis 2000;31:347-82. Weighing in at 35 pages, this is more a reference than a read. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10987697

ERS Task Force Report. Guidelines for management of adult community-acquired lower respiratory tract infections. European Respiratory Society. Eur Respir J 1998;11:986-91. Concise, sensible, well-referenced guideline that places CAP in the context of other LRTI. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9623709

 

Ruiz M, Ewig S, Torres A, et al. Severe community-acquired pneumonia. Risk factors and follow- up epidemiology. AJRCCM 1999;160:923-9. Study out of Barcelona that is the best on this subject in recent years. Key findings were that the epidemiology of severe CAP evolves over time and hence, initial empiric treatment needs to as well. Alcohol abuse was the only independent risk factor for severe CAP, while prior ambulatory antimicrobial therapy was protective, emphasizing the potential benefit of early empiric treatment. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10471620

Ramirez JA, Vargas S, Ritter GW, et al. Early switch from intravenous to oral antibiotics and early hospital discharge: a prospective observational study of 200 consecutive patients with community-acquired pneumonia. Arch Intern Med 1999;159:2449-54. Study found early switch safe and cost-effective.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10665893

Ruiz-Gonzales AM et al. Is Streptococcus pneumoniae the leading cause of pneumonia of unknown etiology? A microbiologic study of lung aspirates in consecutive patients with community-acquired pneumonia. Am J Med 1999;106:385-90. Supports long held belief that most CAP cases of unknown etiology are probably pneumococcal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10225239

Fine MJ, Auble TE, Yealy DM et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. NEJM 1997;336:243-50. Oft-cited prediction rule used in above study by Marrie, et al. incorporates patient demographics, co-morbidities, vitals, labs, and chest film to identify patients likely to do well with outpatient treatment of CAP. Rule difficult to memorize and requires an ABG, but otherwise easy to apply. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8995086

Marrie TJ, Lau CY, Wheeler SL, et al. A controlled trial of a critical pathway for treatment of CAP. CAPITAL Study Investigators. JAMA 2000;283:749-55. Instituting a care pathway for CAP resulted in decreased rates of admission of low-risk patients and shorter hospital stays among those admitted without compromising the care of patients. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10683053

Mundy LM, Leet TL, Darst K, et al. Early mobilization of patients hospitalized with community-acquired pneumonia.  CHEST 2003;124:883-9. A group randomized trial of 458 patients with CAP hospitalized on general medical units found patients undergoing early mobilization had shorter hospital stays without an increase in adverse events compared to usual care. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12970012

Bartlett JG, Gorbach SL. The triple threat of aspiration pneumonia. Chest 1975;68:560-66. Classic review of the presentation, pathophysiology, and natural history of chemical pneumonitis, bacterial pneumonia, and airway obstruction resulting from aspiration of toxic fluids, bacteria, and inert matter respectively. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1175415

Metlay JP, Kapoor WN, Fine MJ. Does this patient have CAP? Diagnosing pneumonia by history and physical examination. JAMA 1997;278:1440-5. Systematic review found H & P do not reliably predict the presence of pneumonia in acutely symptomatic, ambulatory patients. Physicians' interobserver agreement on exam findings is poor. Article highlights the importance of chest x-rays in diagnosis of pneumonia but the optimal strategy for their use remains unclear. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9356004

Mittl RL, Schwab RJ, Duchin JS et al. Radiographic resolution of community-acquired pneumonia. Am J Resp Crit Care 1994;149:630-5. Prospective follow-up of both inpatients and outpatients with diagnosis of CAP is cited as a guide for when to look for endobronchial lesions in the setting of slowly clearing

pneumonia.  The study found age and multilobar disease were independent predictors of delayed resolution.  Radiographic resolution seen in 51% at 2 weeks, 67% at 4 weeks, and 90% at 12 weeks.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8118630

COPD

Overview

Pauwels RA, Buist AS, Calverley PMA et al. Global strategy for the diagnosis, management, and prevention of COPD: GOLD workshop summary. AJRCCM 2001;163:1256-76. Supported by the NHLBI and WHO and endorsed by the ATS, the summary is a bit more flexible than the previous ATS guidelines, places greater emphasis on the use of NIPPV during exacerbations, and has revised recommendations for the use of inhaled corticosteroids. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11316667

Supplemental oxygen

Continuous or nocturnal oxygen therapy in hypoxemic COPD. The NOTT group. Ann Intern Med 1980;93(3):391-8. Famous multicenter study showing use of continuous oxygen therapy (>17 hr/d) resulted in lower mortality than use of nocturnal therapy (12 hr/d) in pts. with PaO2 55 mmHg or PaO2 59 mmHg and pulmonary hypertension, right-sided failure, or Hct 55%. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6776858

Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. MRC Working Party. Lancet 1981;8222:681-5. Another well- known study showing improved survival with continuous oxygen in hypoxemic COPD patients. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6110912

Tiep BL. Oxygen conserving devices. Up to Date, 7/30/99. Practical review of different modes of O2 delivery for LTOT.

O'Donohue W Jr., Tiep BL, Carter R. Long-term supplemental oxygen therapy. Up to Date, 1/16/04. Useful review of the indications and requirements for prescribing long-term oxygen therapy.

Stoller JK. Oxygen and air travel. Respir Care 2000;45:214-21. Summarizes readily available means of assessing travelers' in-flight oxygen needs. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10771793

Survival

Traver GA, Cline MG, Burrows B. Predictors of mortality in COPD: A 15-year f/u study. Amer Rev Res Dis 1979;119:895-902. Ubiquitously-cited study looking at FEV1 and survival. After controlling for age, the FEV1 after bronchodilator was the

best predictor of survival, but was less predictive in patients over 65. The observed wide variability in survival of individual patients with similar initial FEV1 values has important implications for patients considering surgical treatments for their COPD. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=453709

Anthonisen NR. Prognosis in COPD: results from multicenter clinical trials. Am Rev Respir Dis 1989:140:S95-9. This analysis of previous trials found that COPD patients with hypoxemia had worse survival than non-hypoxemic COPD patients with equivalent FEV1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3510578

Inhaled and systemic steroids

Pauwels RA, Lofdahl CG, Laitinen LA, et al. Long-term treatment with inhaled budesonide in persons with mild COPD who continue smoking. NEJM 1999;340:1948-1953. Study of inhaled corticosteroid in smokers with mild COPD showed a modest improvement in FEV1 relative to placebo in the first 6 months, but no benefit during the subsequent 2.5 years. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10379018

Burge PS, Calverley PMA, Jones PW, et al. Randomised, double blind, placebo controlled study of fluticasone proprionate in patients with moderate to severe COPD: the ISOLIDE trial. BMJ 2000;320:1297-1303. Use of inhaled steroid did not improve the rate of decline in FEV1 compared to placebo. The Flovent group had a median of 0.99 exacerbations/yr vs. 1.32/yr in the placebo arm. Response to oral steroids given in the run-in phase was not predictive of subsequent benefit from inhaled steroid. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10807619

The Lung Health Study Research Group. Effect of inhaled triamcinolone on the decline in pulmonary function in COPD. NEJM 2000;343:1902-09. Randomized, controlled study followed over 1000 patients for an average of 4.5 yrs and found no difference in rate of decline in FEV1 in the inhaled steroid group. Patients using triamcinolone had, by some measures, fewer symptoms, but also had a greater rate of decline in bone density that is of unknown clinical significance. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11136260

Fan VS, Bryson CL, Curtis JR, et al. Inhaled corticosteroids in COPD and risk of death and hospitalization. AJRCCM 2003;168;1488-94.  Prospective cohort study of over 8,000 patients from 7 VA medical centers. The authors defined ICS-users as being on medication at least 80% of the time based on pharmacy records and performed a time-dependent analysis to account for changing ICS use over time.  Unlike a number of recent observational studies, this study found the use of ICS was not associated with reduced mortality and exacerbations. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14525798    

van der Valk P, Monninkhof E, van der Palen J, et al. Effect of discontinuation of inhaled corticosteroids in patients with COPD. AJRCCM 2002;166:1358-63. Randomized, blinded, placebo-controlled, single-center study of 244 patients with

a mean FEV1% predicted of 57% found more patients in the placebo arm experienced an exacerbation over a 6-month follow-up period (57 vs. 47%; hazard ratio for 1st exacerbation 1.5 [CI] 1.1-2.5).  Subgroup analysis found benefit derived primarily by patients with baseline FEV1 < 50% predicted. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12406823

Calverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and fluticasone in the treatment of COPD: a RCT. Lancet 2003;361:449-56.  Large study found patients receiving combination therapy had some improvement in symptoms and FEV1 compared to using each component individually, but there was no difference in frequency of exacerbations. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12583942

Niewoehner DE, Erbland ML, Deupree RH, et al. Effect of systemic glucocorticoids on exacerbations of COPD. NEJM 1999;340:1941-7. Multicenter, double-blind, placebo- controlled study found modest benefit to use of high-dose intravenous steroids. Steroid group had fewer treatment failures (combined endpoint of death, need for intubation, readmission, or intensification of pharmacologic therapy), and shorter hospital stays, but the primary benefit was in decreasing the need to intensify therapy with use of open-label steroids. No benefit from steroids was present at 6 months of f/u, and 2 week and 8 week courses were equally effective. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10379017

Role of antibiotics

Anthonisen NR, Manfreda J, Warren CPW et al. Antibiotic therapy in exacerbations of COPD. Ann Intern Med 1987;106:196-204. Famous study often cited by proponents of antibiotic use for COPD exacerbations. Randomized, blinded, controlled study found use of antibiotics in the presence of increased dyspnea, increased sputum production, and increased sputum purulence improved outcomes. The improvement was no longer significant, however, after controlling for use of oral steroids. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3492164

Hirschmann JV. Do bacteria cause exacerbations of COPD? vs. Murphy TF, Sethi S, Niederman MS. The role of bacteria in exacerbations of COPD: A constructive view. Both from CHEST 2000;118:198-209. The articles are presented in a debate format. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10893379

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10893380

Lung volume reduction surgery

Cooper JD, Trulock EP, Triantafillou AN, et al. Bilateral pneumonectomy (volume reduction) for COPD. J Thorac Cardiovasc Surg 1995;109:106-19. This paper revived interest in LVRS for COPD and has generated lots of controversy.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7815786

NETT Research Group. Patients at high risk of death after lung-volume-reduction surgery. NEJM 2001;345:1075-83. Early results from NETT found a 16% 30-day mortality following LVRS in the 69 patients with FEV1 < 20% predicted AND homogenous disease per CT OR DLCO < 20% predicted. This population had higher overall mortality than comparable patients randomized to medical treatment. Survivors of LVRS had modest improvements in exercise tolerance and FEV1, but similar measures of quality of life. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11596586

 

Fishman A, Martinez F, Naunheim K, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema: NETT Research Group. NEJM 2003;348:2059-73.  After excluding the 140 pts identified as having high risk of mortality based on the above interim analysis, a greater proportion of LVRS patients had improved exercise tolerance compared to the medical therapy arm (16% vs. 3%), but there was no survival advantage after 24 months.  Subgroup analysis found patients with predominantly upper lobe disease and low exercise capacity had improved mortality, while patients with non-upper lobe emphysema and high exercise capacity had higher mortality following LVRS compared to medical therapy. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12759479

**See also Lung Cancer, Lung Transplantation, and Non-invasive Mechanical Ventilation

Cough

Irwin RS, Madison JM. The persistently troublesome cough. AJRCCM 2002;165:1469-74. Good review covering the evaluation and treatment of acute, subacute, and chronic cough. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12045118

Cystic Fibrosis

Pryor JA. Physiotherapy for airway clearance in adults. Eur Respir J  1999;14:1418-24.  Somewhat cursory overview of common airway clearance techniques used in the setting of CF, neuromuscular disease, and other diseases associated with impaired secretion clearance. The author also touches on the paucity of evidence supporting the superiority of any one approach.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10624775

Fuchs HJ, Borowitz DS, Christiansen DH, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis: the Pulmozyme Study Group.  NEJM  1994;331:637-42. Large RCT found patients receiving a 24-week course of

Pulmozyme had an improvement in FEV1 of 5% compared to placebo and decreased exacerbation rate (28 vs. 37% in placebo group). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7503821

Ramsey BW, Pepe MS, Quan JM, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. NEJM 1999;340:23-9. Study found use of TOBI on alternating months improved lung function, decreased bacterial burden, and decreased the relative risk of hospitalization. The rate of acquired tobramycin resistance was about 7% over 24 weeks. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9878641

Saiman L, Marshall BC, Mayer-Hamblett N, et al. Azithromycin in patients with cystic fibrosis chronically infected with pseudomonas aeruginosa.  JAMA 2003;290:1749-56.  Large multicenter RCT of 6 months duration found chronic azithromycin resulted in a 4.4% improvement in FEV1% predicted compared to a 1.8% decline in placebo.  The azithromycin group had fewer exacerbations and gained more weight. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14519709

Kerem E, Reisman J, Corey M, et al. Prediction of mortality in pts with cystic fibrosis. NEJM 1992;326:1187-91. Established FEV1 < 30% predicted as the strongest, albeit suboptimal, predictor of mortality.  A clearly superior means of predicting mortality in order to optimize timing of lung transplantation remains elusive. See also Lung Transplantation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1285737

Drug Toxicities

Rosenow EC, Myers JL, Swensen SJ, et al. Drug-induced pulmonary disease: an update. CHEST 1992;102:239-250. Review covering the more common drug toxicities with some degree of categorization by clinical presentation. Almost 10 years old. Keep an eye out for something more recent. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1623761

Web site: www.pneumotox.com

End of Life Care

Withholding and withdrawing life-sustaining therapy. ATS Statement. Am Rev Respir Dis 1991;144:726-31. Statement covers patient autonomy, surrogate decision-making, and futility. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1892317

Tonelli MR. Pulling the plug on living wills. CHEST 1996;110:816-22. Discusses the difficulties and limitations of formulating and applying advanced directives. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8797430

A controlled trial to improve care for seriously ill hospitalized patients. SUPPORT Investigators. JAMA 1995;274:1591-8. This landmark study found interventions to increase physician awareness of prognosis and facilitate communication between physicians and patients or surrogates made no significant difference compared to controls. Preference for CPR was discussed with a minority of patients, physicians often were unaware of their patients' preferences for CPR. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7474243

Luce JM. Making decisions about the forgoing of life-sustaining therapy. AJRCCM 1997;156:1715-8. Commentary that summarizes much of the recent research in this area. Emphasizes the need to reaffirm patient autonomy and to be cautious in the use of "futility" as a reason to withdraw care. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9412545

Prendergast TJ, Claessens MT, Luce JM. A national survey of end-of-life care for critically ill patients. AJRCCM 1998;1163-7. Survey of all U.S. training programs with significant critical care exposure (48% participation) found 38% of dying patients had support withdrawn and only 23% had full ICU care including CPR. Study noteworthy for marked variation in practice between ICUs. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9769276

Truog RD, Cist AFM, Brackett SE, et al. Recommendations for end-of-life care in the intensive care unit: The Ethics Committee of the Society of Critical Care Medicine.  Crit Care Med  2001;29:2332-48.  Recommendations for clinical care of dying patients in the ICU derived from data and expert opinion. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11801837

Hemoptysis

Dweik RA, Stoller JK. Role of bronchoscopy in massive hemoptysis. Clin Chest Med 1999;20:89- 104. Good resource, but does not incorporate chest CT into the evaluation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10205720

 Hirshberg B, Biran I, Glazer M, et al. Hemoptysis: etiology, evaluation, and outcome in tertiary referral hospital. Chest 1997;112:440-44. Large case series from Jerusalem included because few large studies published recently. Study indicates bronchoscopy and chest CT have a complementary role in evaluation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9266882

HIV and Pulmonary Disease

Chin DP, Hopewell PC. Mycobacterial complications of HIV infection. Clin Chest Med 1996;17:697-711. Covers the atypical presentation of TB and atypical mycobacterium in this population. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9016372

Gagnon S, Boota AM, Fischl MA, et al. Corticosteroids as adjunctive therapy for severe PCP in AIDS. NEJM 1990;323:1444-50. One of three studies published in the same year establishing the efficacy of steroids in severe PCP in patients with AIDS. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2233916

Hirschtick RE, Glassroth J, Jordan MC, et al. Bacterial pneumonia in persons infected with the human immunodeficiency virus. Pulmonary Complications of HIV Infection Study Group. NEJM 1995;333:845-51. Part of the landmark PCHIS study, this is the first and best prospective study of CAP in HIV-infected patients. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7651475

Beck JM, Rosen MJ, Peavy HH. Pulmonary complications of HIV infection. Report of the 4th NHLBI Workshop.  AJRCCM  2001;164:2120-6 Summarizes current knowledge of HIV-associated pulmonary diseases since the advent of HAART. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11739145

Interstitial Lung Disease

Overviews

American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias.  AJRCCM 2002;165:277-304. Written to standardize the diagnostic criteria and terminology for idiopathic interstitial pneumonias, this article nicely summarizes the clinical, radiologic, and histologic features of the ILD alphabet soup. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11790668

Mathieson JR, Mayo JR, Staples CA, Muller NL. Chronic diffuse infiltrative lung disease: comparison of diagnostic accuracy of CT and chest radiography. Radiology 1989;171:111-16. First study to assess accuracy of CT-based diagnosis for patients with ILD. Correctly diagnosed UIP in 89% of cases, sarcoid in 77% of cases, and were, for the most part, less accurate in diagnosing less common diseases. Includes an interesting table of the frequency of selected CT findings observed among the 5 most common ILDs in the study (e.g. pleural fluid/thickening seen in only 9% of UIP cases). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2928513

Organizing Pneumonia

Epler GR, Colby TV, McCloud TC, et al. Bronchiolitis obliterans organizing pneumonia. NEJM 1985;312:152-8. Classic article describing idiopathic BOOP (now known as cryptogenic organizing pneumonia) http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3965933

Idiopathic Pulmonary Fibrosis

Douglas WW, Ryu JH, Swensen SJ, et al. Colchicine vs. prednisone in the treatment of IPF: a randomized prospective study. AJRCCM 1998;158:220-5. Study found colchicine and prednisone equally ineffective. Colchicine had less toxicity. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9655733

Ziesche R, Hofbauer E, Wittmann K, et al. A preliminary study of long-term treatment with IFN gamma-1b and low dose prednisolone in patients with IPF. NEJM 1999;341:1264-9. Small study found use of IFN promising in patients with IPF not responding to initial therapy. Results of a multicenter study are pending as of 12/03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10528036

Raghu G, Depaso WJ, Cain K, et al. Azathioprine combined with prednisone in the treatment of IPF. Am Rev Respir Dis 1991;144:291-6. RCT of prednisone plus imuran vs. prednisone alone found some patients had greater benefit with the combination of drugs, but overall differences between groups did not reach statistical significance. Some current trials of new therapies use this combination in the control group.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1859050

Hunninghake GW, Zimmerman MB, Schwartz DA, et al. Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis.  AJRCCM  2001;164:193-6.  Study found pulmonologists and radiologists with expertise in interstitial lung disease reliably made a clinical diagnosis of IPF when compatible clinical and radiologic data were present (only 50% of all IPF cases).  Transbronchial biopsy was helpful in 2% of cases and pathologists did not agree on the histologic diagnosis. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11463586

Sarcoidosis

Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999.. AJRCCM 1999;160:736-55. Comprehensive and relatively readable. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10430755

**See also Pulmonary Hypertension, Lung Transplantation, and Occupational Medicine

Invasive Mechanical Ventilation

Darioli R, Perret C. Mechanical controlled hypoventilation in status asthmaticus. Am Rev Respir Dis 1984;129:385-7. Noteworthy for being the first description of permissive hypercapnea and low tidal volumes during mechanical ventilation of asthmatics high airway pressures. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6703497

Marini JJ, Pierson DJ, and Hudson LD. Acute lobar atelectasis: a prospective comparison of fiberoptic bronchoscopy and respiratory therapy. Amer Rev Resp

Dis 1979;119:971-8. This could be useful in fending off suck bronchs. Study found FOB followed by RT no better than RT alone at 24-48 hours. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=453712

Ely EW, Baker AM, Dunagan DP, et al. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. NEJM 1996;335:1864-9. RCT found protocol of daily weaning parameters followed by trials of spontaneous breathing in appropriate patients and subsequent notification of physicians of successful trials reduced the duration of mechanical ventilation compared to usual care (daily weaning parameters only). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8948561

Esteban A, Frutos F, Tobin MJ, et al. A comparison of four methods of weaning patients from mechanical ventilation. NEJM 1995;332:345-50. Prospective, randomized study found once-daily or multiple daily trials of spontaneous breathing (T-piece or CPAP <5 cm) resulted in more rapid successful extubation than gradual weaning of pressure support or IMV. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7823995

Brochard L, Rauss A, Benito S, et al. Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation. AJRCCM 1994;150:896-903. Prospective, randomized study found weaning with pressure support mode superior to SIMV mode and T-piece trials. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7921460

Yang KL, Tobin MJ. A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. NEJM 1991;324:1445-50. Study in a VA population found the rapid shallow breathing index (RSBI = RR/Vtidal) was the single best predictor of weaning success (sensitivity 0.97, specificity 0.64).   http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2023603

**See also ARDS and Noninvasive Ventilatory Support.

Lung Cancer

Staging

Mountain CF. Revisions in the international system for staging lung cancer. CHEST 1997;111:1710-1717. The staging revisions were made to better group TNM patterns with similar prognosis and approach to treatment. Includes expected survival for clinically and surgically staged cancer at 1 through 5 years. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9187198

Van Tinteren H, Hoekstra OS, Smit EF, et al. Effectiveness of PET in the preoperative assessment of patients with suspected non-small-cell lung cancer: the PLUS multicentre randomised trial.  Lancet 2002;359:1388-93.  Efficacy study found addition of PET to conventional work-up decreased futile thoracotomies and

the combination of PET and conventional workup was 79% sensitive for identifying futile thoracotomies. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11978336

Gould MK, Kuschner WG, Rydzak CE, et al. Test performance of PET and CT for mediastinal staging in patients with non-small-cell lung cancer. Ann Intern Med 2003;139:879-92.  This meta-analysis found a median sensitivity of 85% and specificity of 90% for PET in determining the presence of mediastinal disease in known or suspected NSCLC.  PET's median sensitivity improved to 100% and median specificity fell to only 78% in the presence of lymphadenopathy on CT while PET had a median sensitivity of 82% and median specificity of 93% in the absence of lymphadenopathy. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14644890

Fritscher-Ravens A, Davidson BL, Hauber H, et al. Endoscopic ultrasound, PET, and CT for lung cancer. AJRCCM 2003;168:1293-7. This is the largest study to date comparing PET and endoscopic ultrasound with fine-needle aspiration for staging potentially operable patients with known or suspected lung cancer. PET and ultrasound had similar sensitivity and negative predictive value, but ultrasound had 100% specificity.  A cost-analysis favored endoscopic ultrasound over PET. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12904322

Screening for lung cancer

The following articles are the basis for the belief that screening with CXR and/or sputum cytology does not work. Many have expressed concern about the quality of these studies.

Fontana RS, Sanderson DR, Taylor WF, et al. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study. Am Rev Respir Dis 1984;130:561-5. Also includes a summary of the combined results of the Mayo, Sloan-Kettering, and Johns Hopkins study sites on pp 565-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6091507

Melamed MR, Flehinger BJ, Zaman MB, et al. Screening for lung cancer: results of the Memorial Sloan-Kettering study in New York. CHEST 1984;86:44-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6734291

Frost JK, Ball WC, Levin ML, et al. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study. Am Rev Respir Dis 1984;130:549-54 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6091505

Kubik A, Parkin DM, Khlat M, et al. Lack of benefit from semi-annual screening for cancer of the lung: follow-up of a randomized controlled trial on a population of high-risk males in Czechoslavakia. Int J Cancer 1990;45:26-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2404878

The following articles address screening with chest CT scans.

Henschke CI, McCauley DI, Yankelevitz DF, et al. Early lung cancer action project: overall design and findings from baseline screening. Lancet 1999;354:99-105. Study of annual low dose CT in detecting lung cancer in 1000 heavy smokers identified noncalcified nodules in 23% of patients and 12% of nodules were malignant.  The yield was near miraculous as 27 of 28 biopsies were positive for malignancy, and 87% of these were stage I. Large scale study to confirm findings and assess long-term survival benefit and costs is in progress. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10408484

Swenson SJ, Jett JR, Sloan JA, et al. Screening for lung cancer with low-dose spiral computed tomography. AJRCCM 2002;165:508-13. Unlike the Henschke study above, 66% of 1,520 patients age > 50 and tobacco use > 20 pack-years had one or more non-calcified nodules.  One year after enrollment, 1.7% of enrolled patients were diagnosed with lung cancer (1.1% of all nodules were malignant) and 0.9% of participants were diagnosed with stage IA NSCLC.  Seven of 29 resected nodules were benign. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11850344

Risk factors

Tockman MS, Anthonisen NR, Wright EC, et al. Airways obstruction and the risk for lung cancer. Annals Intern Med 1987;106:512-18. This study found smokers with COPD had about a 5-fold risk of developing lung cancer compared to smokers without COPD. The more severe the COPD, the greater the risk. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3826952

**See also Solitary Pulmonary Nodule

Lung Transplantation

Overviews

International guidelines for the selection of lung transplant candidates. The American Society for Transplant Physicians (ASTP)/American Thoracic Society(ATS)/European Respiratory Society(ERS)/International Society for Heart and Lung Transplantation(ISHLT). AJRCCM 1998;158:335-9. This is an excellent overview of referral criteria for potential lung transplantation candidates. Oh, by the way, this is also the document used for questions on the pulmonary boards regarding referral criteria and absolute contraindications to transplant. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9655748

Arcasoy SM, Kotloff RM. Lung transplantation. NEJM 1999;340:1081-91.

This is a well written concise introduction to transplant ideal for the fellow.  Includes discussions of listing, surgical technique, and post-transplant outcomes as well as a table summarizing the side effects and common drug interactions associated with immunosuppressant medications.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10194239

 

Bronchiolitis obliterans

Estenne M, Hertz MI. Bronchiolitis obliterans after human lung transplantation. AJRCCM 2002;166:440-4. Good review of what is known about bronchiolitis obliterans.  Also discusses the limitations of using the clinical entity “bronchiolitis obliterans syndrome” in the post transplant recipient. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12186817

 

Non-pulmonary complications of lung transplantation

Maurer JR, Tewari S. Nonpulmonary medical complications in the intermediate and long-term survivor. Clin Chest Med 1997;18:367-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9187828

Survival

Hosenpud JD, Bennett LE, Keck BM, et al. Effect of diagnosis on survival benefit of lung transplantation for end-stage lung disease. Lancet 1998;351(9095):24-7. Well-devised analysis of potential survival benefit for patients afflicted with CF, COPD, and IPF listed for transplant by UNOS.  Major limitations are that the paper evaluates outcomes from more than 10 years ago and listing practice assumptions from the model may not hold true at this time. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9433425  

De Meester J, Smits JM, Persijn GG, et al. Listing for lung transplantation: life expectancy and transplant effect, stratified by type of end-stage lung disease, the Eurotransplant experience. J Heart Lung Transplant 2001;20:518-24. Analysis of survival benefit using the Eurotransplant wait list and post transplant survival. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11343978

Future directions

Gerhardt SG, McDyer JF, Girgis RE, et al. Maintenance azithromycin therapy for bronchiolitis obliterans syndrome: results of a pilot study. AJRCCM 2003;168:121-5. Interesting pilot study found chronic macrolide therapy improved the FEV1 in 5 of 6 patients with bronchiolitis obliterans syndrome.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12672648

Johnson BA, Iacono AT, Zeevi A, et al. Statin use is associated with improved function and survival of lung allografts. AJRCCM 2003;167(9):1271-1278. Although this is a non-randomized, retrospective study, the rigorous analysis, improved

outcomes, and the postulated mechanism of benefit for this drug class make the findings provocative. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12615629

Goldfarb NS, Avery RK, Goormastic M, et al. Hypogammaglobulinemia in lung transplant recipients. Transplantation 2001;71(2):242-246. This retrospective single-institution review of 67 patients found IgG deficiency is common in post-transplant patients and is associated with increased risk of infection and decreased survival. It remains to be seen if altering treatment to improve IgG has an effect on subsequent risk for infection. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11213067

**See also Arcasoy et al under Pulmonary Hypertension

Noninvasive Ventilatory Support

In COPD

Brochard L, Mancebo J, Wysocki M, et al. Noninvasive ventilation for acute exacerbations of COPD. NEJM 1995;333:817-22. Landmark prospective, randomized study found use of NIPPV in selected patients with COPD exacerbations resulted in fewer intubations, complications, days in hospital, and lower in-hospital mortality compared to standard treatment. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7651472

Nava S, Ambrosino N, Clini E, et al. Non-invasive mechanical ventilation in the weaning of patients with respiratory failure due to chronic obstructive pulmonary disease. Ann Intern Med 1998;128:721-8. Oft-cited RCT included 50 patients intubated for a COPD exacerbation who failed a T-piece trial.  Patients randomized to immediate extubation to NIPPV had decreased duration of mechanical ventilation and improved survival compared to the control group undergoing PS wean with twice daily spontaneous breathing trials. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9556465

In hypoxemic respiratory failure (all types):

Declaux C, L'Her E, Alberti C, et al. Treatment of acute hypoxemic nonhypercapnic respiratory insufficiency with CPAP delivered by face mask. JAMA 2000;284:2352-60. Prospective, randomized, multicenter study compared oxygen to oxygen plus CPAP in this population (123 patients;17% cardiac etiology, 83% ALI). Study found no difference in the need for intubation, lenghth of hospital stay, or hospital mortality, and the CPAP group had an increased incidence of adverse events. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11066186

Antonelli M, Conti G, Rocco M, et al. A comparison on NIPPV and conventional mechanical ventilation in patients with acute respiratory failure. NEJM 1998;339:429-35. Randomized study compared NIPPV with immediate intubation and conventional ventilation in 64 patients with acute, non-hypercapnic, hypoxemic respiratory failure (19% cardiogenic and 25% ARDS).  Use of NIPPV resulted in gas exchange and survival comparable to conventional ventilation but

was associated with fewer serious complications and shorter ICU stays. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9700176

Ferrer M, Esquinas A, Leon M, et al. Non-invasive ventilation in severe hypoxemic respiratory failure: a randomized clinical trial. AJRCCM 2003;1681140-44. Study of 105 non-hypercapneic patients found NIPPV decreased need for intubation and improved 90-day survival compared to oxygen therapy alone.  Subgroup analysis found the 34 patients with pneumonia had the greatest benefit while mask ventilation did not appear to reduce the need for intubation in patients with ARDS and cardiogenic edema. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14500259

In cardiogenic hypoxemic respiratory failute:

Bersten AD, Holt AW, Vedig AE, et al. Treatment of severe cardiogenic pulmonary edema with CPAP delivered by face mask. NEJM 1991;325:1825-30. Randomized study of 39 patients with hypercapnic cardiogenic respiratory failure found use of CPAP plus oxygen resulted in better gas exchange in the first 24 hours and less need for intubation than use of oxygen alone. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1961221

Masip J, Betbese AJ, Paez J, et al. Non-invasive pressure support ventilation versus conventional oxygen therapy in acute cardiogenic pulmonary oedema: a randomized trial.  Lancet 2000;356:2126-32. Study of 37 patients (of whom 43% had hypercapnia) found pressure support by mask reduced the need for intubation (5% vs. 33%).  There was no difference in duration of hospital admission or mortality. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11191538

Nava S, Carbone G, DiBattista, N, et al. Non-invasive ventilation in cardiogenic pulmonary edema: a multicenter randomized trial.  AJRCCM 2003;168:1432-7.  This larger study (130 patients) found non-invasive pressure support did not improve outcomes compared to conventional therapy.  Mask ventilation reduced intubations in the 64 patients with PaCO2 > 45 mmHg (6% vs. 29%), but this difference was not significant after regression analysis. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12958051

In neuromuscular weakness

Benditt JO. Management of pulmonary complications in neuromuscular disease. Phys Med Rehab Clin 1998;9:167-85. Nice review of negative and positive pressure ventilation, indications, costs, and benefits of initiating ventilation in this population. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9894139

Occupational Medicine

Asthma/RADS

Blanc PD, Toren K. How much adult asthma can be attributed to occupational factors? Am J Med 1999;107:580-7. Based on a critical review and synthesis of the published literature, the authors estimate occupational factors are associated with 10% of adult asthma cases. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10625027

Burge PS, O’Brien IM, Harries MG. Peak flow rate records in the diagnosis of occupational asthma due to isocyanates. Thorax 1979;34:317-24.  Landmark study was the first to show peak flow is a suitable alternative to provocation testing in the diagnosis of OA. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=483205

Charous BL, Blanco C, Tarlo S, et al. Natural rubber latex allergy after 12 years: recommendations and perspectives. J Allergy Clin Immunol 2002;109:31-4. Reviews the relationship between exposure to powdered natural rubber latex gloves and asthma and makes recommendations for non-powdered gloves. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11799362

Brooks SM, Weiss MA, Bernstein IL. Reactive airways dysfunction syndrome (RADS): persistent asthma syndrome after high level irritant exposures. CHEST 1985;88:376-84. Landmark article describing 10 patients in which the term “RADS” was coined.   In the majority of cases respiratory symptoms and hyperreactivity persisted for greater than 1 year after a large exposure to vapor, fumes, or smoke.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=4028848 

Zock JP, Jarvis D, Luczynska C, et al. Housing characteristics, reported mold exposure, and asthma in European Community Respiratory Health Survey. J Allergy Clin Immunol 2002;110:285-92. Multicenter study looked at the association between mold exposure (based on questionnaire) and asthma (based on symptoms and methacholine challenge) and concluded that mold growth has an adverse effect on adult asthma. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12170270 

Associations with interstitial lung disease and neoplasia

Selikoff IJ, Hammond EC, Churg J. Asbestos exposure, smoking, and neoplasia. JAMA 1968;204:106-12. Landmark study showing the synergistic effect of smoking and asbestos exposure on developing lung cancer.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=5694532

Wagner JC, Sleggs CA, Marchand P. Diffuse pleural mesothelioma and asbestos exposure in the NW Cape Province. Br J Ind Med 1960;17:260-71. Landmark study linking mesothelioma to asbestos exposure.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=13782506

Adverse effects of crystalline silica exposure. American thoracic society committee of the scientific assembly on environmental occupational health. AJRCCM 1997;155:761-8. Reviews the epidemiology and prevention of silica-associated lung diseases including silicosis, asthma, tuberculosis, and

extrapulmonary diseases. This document is also available in UpToDate. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9032226

Rossman MD, Kern JA, Elias JA, et al. Proliferative response of bronchoalveolar lymphocytes to beryllium. A test for chronic beryllium disease. Ann Intern Med 1988;108:687-93. Article noteworthy for establishing the use of the lymphocyte proliferation test in the diagnosis of chronic beryllium disease. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3282464

Infante PF, Newman LS. Beryllium exposure and chronic beryllium disease. Lancet 2004;363:415-6. The authors highlight the lack of adequate protection for workers, the underdiagnosis of CBD by providers, and the growing number of industries in which exposure occurs. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14962519

 

Parapneumonic Effusion

Light RW, MacGregor MI, Luchsinger PC, et al. Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med 1972;77:507-13. This paper is the basis for using pleural fluid LDH and protein to classify effusions as transudative or exudative. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=4642731

Light RW, Girard WM, Jenkinson SG, et al. Parapneumonic effusions. Amer J Med 1980;69:507-12. The notion that a parapneumonic effusion with pH less than 7.0 or glucose < 40mg/dl is "complicated" and requires drainage is derived from this study. Study included a total of 10 patients (7 with + cultures, 3 with pus). 6 of 10 met the pH criteria and 7 of 9 met the glucose criteria. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7424940

Berger HA, Morganroth ML. Immediate drainage is not required for all patients with complicated parapneumonic effusions. CHEST 1990;97:731-5. Oft-cited retrospective study found 13 of 16 patients with complicated effusions (defined as pH < 7.2 or positive GS or positive culture, but without pus present) had resolution of effusions with antibiotics alone. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2306975

Bouros D, Schiza S, Siafakas N. Utility of fibrinolytic agents for draining intrapleural infections. Sem Resp Infect 1999;14:39-47. Reviews the somewhat limited data indicating use of lytics decreases the need for surgery compared to chest tube drainage alone in patients with empyema and complicated effusions. Patients successfully managed without surgery about 85% of time. Chest tube patency maintained with qid NS flushes in successful trials. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10197396

Wait MA, Sharma S, Hohn J, Dal Nogare A. A randomized trial of empyema therapy. CHEST 1997;111:1548-51. Only randomized trial comparing immediate VATS to tube thoracostomy plus 3 days of daily SK (only 20 patients total). The surgical group had better primary treatment success and earlier hospital discharge, but outcomes of patients randomized to chest tube/lytics was much worse than other reported series, suggesting suboptimal management of those patients. All medical failures were salvageable with VATS. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9187172

Davies CWH, Kearney SE, Gleeson FV, Davies RJO. Predictors of outcome and long-term survival in patients with pleural infection. AJRCCM 1999;160:1682-87. In the absence of frank empyema, tube thoracostomy plus lytics had a PPV of 93% for successful treatment (i.e. no need for surgery). The presence of pus had a PPV for failure of medical management of 26%. Fluid characteristics, effusion size, and degree of pleural thickening were not predictive of medical failure. Study didn't consider presence of loculations or assess long-term outcomes. In part included because it is a good model of how to optimally manage patients when electing to use chest tube drainage rather than VATS. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10556140

Ashbaugh DG. Empyema thoracis. Factors influencing morbidity and mortality. Chest 1991;99:1162-5. Study of 122 consecutive patients looked at the morbidity and mortality of delaying treatment of empyema. Waiting more than 3 days to place a chest tube, and more than 14 days to proceed to surgical drainage when chest tubes fail, was associated with increased morbidity and mortality. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2019172

Colice GL, Curtis A, Deslauriers J, et al. Medical and surgical treatment of parapneumonic effusions. CHEST 2000;188:1158-71. "Evidence-based" guideline derived from relatively low quality evidence reflective of above references. Tables summarize study designs, patient populations, and outcomes of the better studies. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11035692

 Pre-op Pulmonary Assessment   

Bolliger CT, Perruchoud AP. Functional evaluation of the lung resection candidate. Eur Respir J 1998;11:198-212. Good summary of use of PFTs, split function tests, and exercise tests to assess operative risk of lung resection. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9543294

Pollock M, Roa J, Benditt JO, et al. Estimation of ventilatory reserve by stair climbing: a study in patients with chronic airflow obstruction. Chest 1993;104:1378-83. Study found linear increases in VO2 and Ve with stair climbing. In order to reach a VO2 of 20ml/kg/min, subjects had to walk 4.6 flights of stairs, suggesting the tradition of walking patients up one or two flights is an inadequate stress to predict tolerance of surgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8222791

Thoren L. Post-operative pulmonary complication: observations on their prevention by means of physiotherapy. Acta Chir Scand 1954;193-205. Pioneering study on the prevention of post-op pulmonary complications found initiation of chest PT prior to surgery was superior to exclusively post-operative therapy, which in turn was better than no therapy.

Procedures

Bronchoscopy

Cowl CT, Prakash UBS, Kruger BR. The role of anticholinergics in bronchoscopy. CHEST 2000;118:188-92. RCT found anticholinergics did not improve secretions, reduce the need for topical anesthetic, or improve patient comfort. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10893378

Wang KP. Transbronchial needle apiration and percutaneous needle aspiration for staging and diagnosis of lung cancer. Clin Chest Med 1995;16:535-52. Focuses on the nuts and bolts of the technique rather than indications, yield, and risks. Diagrams of endobronchial landmarks for different nodes may be of practical use just prior to procedure. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8521707

Weiss SM, Hert RC, Gianola FJ et al. Complications of fiberoptic bronchoscopy in thrombocytopenic patients. Chest 1993;104:1025-8. Established safety of transnasal bronchs in thrombocytopenic patients. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8404159

Herth FJF, Becker HD, Ernst A.  Aspirin does not increase bleeding complications after transbronchial biopsy. CHEST 2002;122;1461-4 Prospective study compared 285 patients taking ASA within 24 hrs of TBB to 932 non-ASA users and found no difference in the risk of minor, moderate, or major bleeding. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12377879     

Chest Tubes

Gilbert TB, McGrath BJ, Soberman M. Chest tubes: indications, placement, management, and complications. J Intensive Care Med 1993;8:73-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10148363

Pleural Biopsy, Percutaneous

Schwartz ML, Sessler CN. When-and how- to perform percutaneous pleural biopsy. J Respir Dis 1991;12:1155-69. Offers a nice summary of the role of biopsy in the diagnosis of tuberculous and malignant effusions and reviews biopsy technique with Abrams and Cope needles.  See also Light’s textbook “Pleural Diseases” if you do not have access to this journal.    **See also Tuberculosis

Thoracentesis

Jones PW, Moyers JP, Rogers JT et al. Ultrasound-guided thoracentesis: is it a safer method? CHEST 2003;123:418-423. Prospective descriptive study of 605 patients referred for a total of 941 ultrasound-guided thoracenteses.  2.5% sustained a pneumothorax of whom a third received a chest tube; this is a lower incidence than most reported studies without ultrasound guidance, but all procedures were performed by 7 experienced interventional radiologists.  As with previous studies, the yield of routine post-procedure films was low in asymptomatic patients; 3 of 907 had a pneumothorax managed with a chest tube.  Of note, 2 of 373 patients (0.5%) developed re-expansion pulmonary edema following removal of > 1 liter of fluid.  Investigators terminated fluid removal if the patient developed dyspnea or excessive cough.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12576360

Sallach SM, Sallach JA, Vasquez E, et al. Volume of pleural fluid required for diagnosis of pleural malignancy.  CHEST 2002;122:1913-17 In this retrospective case series, the yield of thoracentesis for the diagnosis of malignancy was independent of the volume of fluid collected.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12475826

Pulmonary Embolism

Diagnosis:

PIOPED Investigators. Value of the ventilation/perfusion scan in pulmonary embolism: results of the PIOPED. JAMA 1990;263:2753-2759. This ubiquitously-cited study found that VQ scans are useful when they are high probability and normal, but that most of the time PE can't be ruled in or out by VQ scan. Includes a useful table comparing clinical suspicion and VQ scan result relative to PA gram result. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2332918

Wells PS, Ginsberg JS, Anderson DR, et al. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Ann Intern Med 1998;129:997-1005. Study used a "minimally invasive" approach to managing patients with suspected PE, emphasizing use of serial dopplers rather than PA grams in patients with a non-diagnostic initial work-up. Approach is comparable to the 1999 ATS guidelines; it does not include CT angiography. A particular strength of the study was the use of set criteria to establish clinical suspicion. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9867786

Wells PS, Anderson DR, Rodger M, et al. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer. Ann Intern Med 2001;135:98-107.  Large prospective cohort study using the SimpliRED d-dimer assay (which has sensitivity lower than, and specificity higher than, most other d-dimer tests) found the combination of a low clinical suspicion for PE and a negative d-dimer safely ruled out pulmonary embolism without additional testing. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11453709

Rathbun SW, Raskob GE, Whitsett TL. Sensitivity and specificity of helical CT in the diagnosis of pulmonary embolism: a systematic review. Ann Intern Med 2000;132:227-32. This systematic review concluded 1) the methodology of published studies is poor. 2) compared to pulmonary angiography, sensitivity of helical CT ranged between 53 and 100% and specificity 81 to 100%. 3) studies had limited follow-up of patients with a negative CT. 4) CT can provide alternative diagnosis in up to 33% of cases. 5) abnormal scans effectively rule in P.E. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10651604

Musset D, Parent F, Meyer G, et al. Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study. Lancet 2002;360:1914-20 This prospective cohort study found the combination of a good quality negative CT and negative lower extremity ultrasound safely excluded PE in outpatients with low or moderate clinical probability (0.8% diagnosed with PE during follow-up). Among inpatients, 4.8% with negative CT and ultrasound were diagnosed with PE, or possibly had a PE, during follow-up.  Of note, 15% of patients diagnosed with PE had a negative CT but positive ultrasound.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12493257

Oudkerk M, van Beek EJ, Wielopolski P, et al. Comparison of contrast-enhanced magnetic resonance angiography and conventional pulmonary angiography for the diagnosis of pulmonary embolism: a prospective study. Lancet 2002;359:1643-7.  MRA is a potentially attractive alternative in the substantial number of patients with a non-diagnostic work-up and a contraindication to CT angiogram. This study included 118 unselected patients with non-diagnostic perfusion scans who all underwent MRA and PA-grams.  MRA had a sensitivity of 77% and specificity 98% with higher sensitivity for central clot. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12020524

Dalen JE, Banas JS, Brooks HL, et al. Resolution rate of acute pulmonary embolism in man. NEJM 1969;280:1194-99. This retrospective case series of non-consecutive patients is the basis for the belief that use of pulmonary angiogram for the diagnosis of PE is not compromised if performed within 7 days of presentation. Most patients had a large PE and use of anticoagulation was sporadic. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=5767460

Nicod P, Peterson K, Levine M, et al. Pulmonary angiography in severe chronic pulmonary hypertension. Ann Intern Med 1987;107:565-568. This study established the safety of angiography in patients with chronic, severe pulmonary hypertension. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3631791

Treatment

Hermann RE, Davis JH, Holden WD. Pulmonary embolism: a clinical and pathologic study with emphasis on the effect of prophylactic therapy with anticoagulants. Amer J Surg 1961;102:19-28. Study helped establish anticoagulation as the standard of care for the treatment of PE. The 40% mortality from embolism in this series likely reflects the ability to detect only larger emboli at that time. Regardless, this high mortality has been cited as the rationale for anticoagulation.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=13713631

Schulman S, Granqvist S, Holmstrom M, et al. The duration of oral anticoagulation after a second episode of venous thromboembolism. NEJM 1997;336:393-98. Randomized trial comparing anticoagulation for 6 months compared to indefinitely in patients with a history of recurrent embolism (including idiopathic and with risk factors). Recurrent thromboembolism occurred in 21% of patients in the 6 month group and in 2.7% of the indefinite group after 4 yrs of f/u. Major bleeding occurred in 5% of patients of whom 18% died. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9010144

Agnelli G, Prandoni P, Becattini C, et al. Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Ann Intern Med. 2003;139:19-25. Randomized, non-blinded study of extending anticoagulation beyond 3 months in patients with first episode of idiopathic PE and PE associated with temporary risk factors. Extending anticoagulation in patients with idiopathic PE from 3 to 12 months only delayed onset of what proved to be a high recurrence rate (4-5% per patient-year once off anticoagulation).  Findings highlight the need for new ways of identifying patients at high risk of recurrence so that they can receive indefinite anti-coagulation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12834314

Konstantinides S, Geibel A, Heusel G, et al. Heparin plus altepase compared with heparin alone in patients with submassive pulmonary embolism. NEJM 2002;347:1143-50. Randomized, double-blind study found lytic therapy in submassive PE did not improve mortality.  Patients randomized to lytics were significantly less likely than the placebo group to require escalation of therapy, which primarily entailed administration of lytics.  The indication for rescue therapy was worsening respiratory symptoms, short of intubation, two-thirds of the time. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12374874

 Prevention with vena caval filters.

Streiff MB. Vena caval filters: a comprehensive review. Blood 2000;95:3669-77. Excellent review of the data available on each of the commonly placed filters, including efficacy and rate of complications. A more recent update on the use of retrievable filters is needed. The author notes the paucity of randomized trials and lack of long-term follow-up in existing studies, addresses the controversies surrounding caval filters, and offers recommendations. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10845895

Decousus H, Leizorovicz A, Parent F, et al. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal DVT. NEJM 1998;338:409-15. This is the only randomized trial involving filters. All patients were aniticoagulated and LMW and unfractionated heparin were equally effective. 4.8% of patients receiving anticoagulation alone had PE vs. 1.1% in filter + anticoagulation group at study day 12. There was no difference in rate of PE after anticoagulation was discontinued, but the filter group had significantly more recurrent DVT. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9459643

Thromboendarterectomy for chronic thromboembolic disease

Snyder WA, Kent DC, Baisch BF. Successful endarterectomy of chronically occluded pulmonary artery: clinical report and physiologic studies. J Thorac Cardiovasc Surg 1963;45:482-9. This, and the Moser article below, are the first reports of the procedure. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=13993170

Moser KM, Rhodes G, Hufnagel CC. Chronic unilateral pulmonary artery thrombosis: successful thromboendarterectomy with 30 month follow-up. NEJM 1965;272:1195-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14284991

Jamieson SW, Kapelanski DP, Sakakibara N, et al. Pulmonary endarterectomy: experience and lessons learned in 1,500 cases.  Ann Thorac Surg 2003;76:1457-64. Summarizes entire UCSD experience with thromboendarterectomy.  The most recent 500 cases (through 12/02) are discussed in greater detail.  30-day mortality in this group was 4.4%, which varied according to type of thrombotic lesion and preoperative hemodynamics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14602267

Pulmonary Function Testing

General reviews

Clinics in Chest Medicine, volume 22, number 4, December 2001 contains reviews on the measurement and interpretation of the entire spectrum of pulmonary function testing.  A particular strength is the discussion of how the pathophysiologic changes associated with various disease states are reflected in studies of pulmonary function.

Exercise Testing

Weisman IM, Zeballos RJ. Clinical exercise testing. Clin Chest Med 2001;22:679-701. The focus is on cardiopulmonary exercise testing, but this review also briefly summarizes the 6-minute walk, testing for exercise-induced bronchoconstriction, and cardiac stress testing.  An excellent starting point for the novice. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11787659

ATS/ACCP Statement on cardiopulmonary exercise testing. AJRCCM 2003;167:211-77.  Somewhere between a textbook and a clinical review, this article provides more details on CPET than the above Weisman article.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12524257

 

Pulmonary Hypertension

Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) and conventional therapy for primary pulmonary

hypertension. NEJM 1996;334:296-301. RCT found the epoprostenol group had improved hemodynamics, quality of life, and survival. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8532025

Rich S, Kaufman E, Levy PS. The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. NEJM 1992;327:76-81. Study with suboptimal design but convincing hemodynamic data found improved survival and is the basis for use of CCBs in patients with a good response to vasodilators. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1603139

Badesch DB, Tapson VF, McGoon MD, et al. Continuous intravenous epoprostenol for pulmonary hypertension due to scleroderma spectrum of disease. Ann Intern Med 2000;132:425- 34. Noteworthy for showing benefit from prostacyclin in patients with a secondary cause of pulmonary hypertension.  RCT found prostacyclin improved exercise tolerance, modestly reduced PA pressures, and improved dyspnea scores in some patients, but was associated with frequent side effects and more adverse events. No difference in survival but trial was only of 12 weeks duration. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10733441

Channick RN, Simonneau G, Sitbon O, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomized placebo-controlled study.  Lancet 2001;358:1119-23  First study of chronic bosentan in 32 patients with primary or scleroderma-related pulmonary hypertension.  Over the 12 weeks of the study, bosentan was well-tolerated and improved cardiac index and exercise capacity (70 meter gain in 6-minute walk). Similar results were obtained in a subsequent larger study of 213 patients (Rubin LJ et al. NEJM 2002;346:896-903). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11597664

Arcasoy SM, Christie JD, Ferrari VA, et al. Echocardiographic assessment of pulmonary hypertension in patients with advanced lung disease. AJRCCM 2003;167:735-40.  The cardiology literature indicates echocardiography-derived estimates of pulmonary artery pressures are accurate. This study found 52% of echo estimates were inaccurate (off by > 10 mmHg) in 166 lung transplant candidates and the difference was > 20 mmHg in 28%.  In patients without hypertension, echo was more likely to overestimate pressures while in patients with pulmonary hypertension, it was as likely to over as underestimate.  Accuracy and ability to obtain an estimate varied with the underlying disease. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12480614

 

Sleep Medicine

Sleep Disordered Breathing

Sullivan CE, Berthon-Jones M, Issa FQ et al. Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares. Lancet 1981 April 18;1(8225):862-5. First description of CPAP in the treatment of OSA.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6112294

Iber C, O'Brien C, Schluter J, et al.  Single night studies in obstructive sleep apnea.  Sleep 1991;14:383-385. Contrary to the accompanying editorial, this study first documented the effectiveness of split-night studies for the evaluation of OSA and helped establish split-night studies as the standard of care.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1759089. 

Flemons WW, Littner MR, Rowley JA, et al.  Home diagnosis of sleep apnea:  A systematic review of the literature.  CHEST 2003;124:1543-79.  A summary of where we are with out-of-lab diagnosis of sleep disordered breathing.  Although the effectiveness of these methods may be improving, the appropriate usefulness is a moving target as technology advances faster than the publications that follow. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=Search&DB=PubMed

Schwab RJ, Pasirstein M, Pierson R, et al. Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging.  AJRCCM 2003;168:522-30.  Elegant publication demonstrating the anatomy behind sleep disordered breathing – how can a patient with a normal BMI have OSA?  How can an overweight patient not have OSA?  Don’t miss the online supplement.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12746251

Shahar E, Whitney C, Redline S, et al.  Sleep-disordered breathing and cardiovascular disease. Cross-sectional results of the Sleep Heart Health Study. AJRCCM 2001;163:19-25.     One of a number of important articles derived from the landmark Sleep Heart Health Study, this study found even mild OSA (apnea-hypopnea index of ≥ 11) confers a 2.38 relative risk of self-reported CHF independent of other known risk factors.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11208620

Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study: Sleep Heart Health Study. JAMA 2000;283:1829–1836. This landmark study demonstrated that sleep disordered breathing confers a higher risk of hypertension, independent of age, sex, race, weight, BMI, neck circumference, waist-to-hip ratio, alcohol, smoking, favorite NFL team….http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10770144

Peppard PE, Young T, Palta M, et al.  Prospective study of the association between sleep-disordered breathing and hypertension.  NEJM 2000;342:1378–84. Even more convincing is the Wisconsin Sleep Cohort Study that demonstrated an independent dose-response relation between sleep-disordered breathing at baseline and the development of new hypertension 4 years later.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10805822

Peker Y, Hedner J, Kraiczi H, et al.  Respiratory disturbance index: an independent predictor of mortality in coronary artery disease. AJRCCM 2000;162:81-6. Small (59 patients) prospective study with 5 years of follow-up found patients with untreated OSA and coronary artery disease were at increased on cardiovascular

death.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10903224

Parasomnias

Schenck CH, Bundlie SR, Ettinger MG, et al.  Chronic behavioral disorders of human REM sleep: a new category of parasomnia.  Sleep 2002;9:293-308. The first description of REM Behavior Disorder.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11902435

Circadian Rhythm Disorders

Ancoli-Israel S, Cole R, Alessi C, et al. The role of actigraphy in the study of sleep and circadian rhythms.  Sleep 2003;26:342-92.  This review summarizes the role of actigraphy in the evaluation of patients with insomnia and circadian rhythm disorders.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12749557

Restless Legs Syndrome

Earley, CJ.  Restless legs syndrome.  NEJM  2003;348:2103-9.  RLS – easy to diagnose, easy to treat, and your patients will think you are a genius and be forever grateful.  This review covers the topic well. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12761367

 

Solitary Pulmonary Nodule

Ost D, Fein AM, Feinsilver SH. The solitary pulmonary nodule. NEJM 2003;348:2535-42. Concise review of risks and yield of the currently used diagnostic modalities, including PET scans.  Unlike some recently published guidelines, the authors consider both clinical suspicion for malignancy and operative risk in making management recommendations.  The authors advocate the use of serial CT scans in patients with low probability of cancer as well as patients with intermediate probability with negative additional workup. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12815140

Swenson SJ, Silverstein MD, Ilstrup DM et al. The probability of malignancy in solitary pulmonanary nodules. Arch Int. Med 1997;157:849-855. Authors developed a prediction model for likelihood of malignancy in indeterminant 4-30mm SPNs. Age, cigarette use, hx of any cancer more than 5 years previously, diameter of SPN, spiculation, and upper lobe location were independent predictors of malignancy. Article includes a table with the odds a SPN is malignant based on the above factors. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9129544

Torrington KG, Kern JD. The utility of fiberoptic bronchoscopy in the evaluation of the solitary pulmonary nodule. CHEST 1993;104;1021-1024. Study found low yield for use of FOB in the work-up of radiographic Stage I lung cancer. FOB confirmed

the diagnosis of cancer in 30% of cases (no higher yield with use of fluoroscopic guidance), but this did not affect surgical management. Unsuspected synchronous tumor found in only 1% of cases. Study population skewed in that a high proportion (87%) of SPNs were malignant. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8404158

**See also screening screening under Lung Cancer

Tuberculosis

ATS Statement: Targeted tuberculin testing and treatment of latent tuberculosis infection. AJRCCM 2000;161:S221-S247. Emphasizes restricting testing to patients you intend to treat if positive and defines positive for patients with different risk factors. Recommended duration of INH increased to 9 months. Significant risk of hepatotoxicity with combination INH and rifampin reported since this statement published. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10764341

International Union Against Tuberculosis Committee on Prophylaxis. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. Bull WHO 1982;60:555-64. Noteworthy for being the only study of the efficacy and safety of different durations of INH prophylaxis. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6754120

Stead WW. Management of health care workers after inadvertent exposure to TB: a guide for the use of preventive therapy. Ann Intern Med 1995;122:906-12. Based on early TB outbreaks and more recent studies of health care and nursing home exposures, the author makes recommendations for the management of health care workers with heavy exposure to active disease. Specifically, workers with prior positive PPD do not need treatment unless they become symptomatic per the author. Skin test negative workers should receive INH prophylaxis until they are tested for conversion 8 weeks after exposure. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7755225

Blumberg HM, Burman WJ, Chaisson RE, et al. ATS/CDC/IDSA: Treatment of tuberculosis. AJRCCM 2003;167:603-662. Comprehensive consensus guide to treatment. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12588714

Bock NN, McGowan JE, Ahn J, et al. Clinical predictors of tuberculosis as a guide for respiratory isolation policy. AJRCCM 1996;154:1468-72. Study found upper lobe infiltrate, presence of cavity, self- report of prior positive PPD, and history of TB exposure were predictive of active disease while history of INH prophylaxis was negatively predictive. Basing isolation solely on these criteria, however, would have resulted in 19% of active cases not being isolated. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8912766

ATS Workshop: Rapid diagnostic tests for tuberculosis: what is the appropriate test? AJRCCM 1997;155:1804-14. The article focuses on the indications and limitations to use of direct amplification tests (DAT) for rapid diagnosis of TB in

smear-positive and smear-negative cases. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9154896

Roth BJ. Searching for tuberculosis in the pleural space. CHEST 1999;116:3-4. Reviews use of ADA in work-up of pleural TB. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10424494  http://www.chestjournal.org/cgi/content/full/116/1/3

Kirsch CM, Kroe DM, Azzi RL, et al. The optimal number of pleural biopsy specimens for a diagnosis of tuberculous pleurisy. CHEST 1997;112:702-6. Single institution, mostly retrospective study of 30 patients with proven pleural TB found sensitivity of 87% when a single specimen was sent for culture and the remaining 3 to 9 were sent for histology. Only 40% of submitted samples actually contained pleura, and the diagnostic yield was 100% in the 18/30 patients with more than 6 specimens submitted. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9315802

Conde MB, Loivos AC, Rezende VM, et al. Yield of sputum induction in the diagnosis of pleural tuberculosis.  AJRCCM  2003;167:723-5  Prospective study of 84 patients with pleural tuberculosis found induced sputum culture was helpful in patients with no infiltrate on CXR; 55% of patients with effusion and clear CXR were culture positive, although only 12% had a rapid diagnosis via positive smears. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12598215

**See also section for mycobacterial disease in HIV infection.

Ventilator-associated Pneumonia

Fagon J, Chastre J, Wolff M, et al. Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia. Ann Intern Med 2000;132:621-30. Randomized study found use of BAL or PSB to dictate antibiotic treatment in suspected VAP resulted in lower mortality at 14 days and less antibiotic use compared to standard approach of clinical impression coupled with endotracheal aspirates. Initiation of antibiotic treatment for VAP was withheld until after obtaining specimens and antibiotics were stopped if cultures were negative. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10766680

Chastre J, Fagon J, Bornet-Lesco M, et al. Evaluation of bronchoscopic techniques for the diagnosis of nosocomial pneumonia. AJRCCM 1995;152:231-240. Study compared immediate post-mortem BAL and PSB to lung biopsy histology and culture and found bronchoscopic specimens had a sensitivity of 82-91% and specificity of 78-89% compared to the gold standard of lung biopsy cultures, provided patients had no recent antibiotic changes prior to death and had not developed pneumonia prior to the terminal phase of their disease. Pertinent in that the above study by Fagon et al is predicated on the belief that BAL and PSB accurately diagnose VAP. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7599829

Kirtland SH, Corley DE, Winterbauer RH, et al. The diagnosis of VAP: a comparison of histologic, microbiologic, and clinical criteria. CHEST 1997;112:445-57. Study

with a similar design to the Chastre study but without restrictions on use of antibiotics or recent pneumonia. Authors found poor correlation between histologic findings and quantitative cultures from bronch specimens. Tracheal aspirates were 87% sensitive but 31% specific compared to biopsy culture. A sterile BAL had a PPV of 91% for sterile lung parenchyma. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9266883

Kollef MH. The prevention of ventilator-associated pneumonia. NEJM 1999;340:627-634. Makes recommendations for or against known preventive strategies and grades the quality of data supporting each intervention. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10029648

Drakulovic MB, Torres A, Bauer TT, et al. Semirecumbancy to prevent VAP. Lancet 1999;354:1851-8. Study found supine position is an independent risk factor for VAP and positioning at 45 reduces the risk, especially if patient receiving tube feeds. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10584721

Cook DJ, Walter SD, Cook RJ, et al. Incidence of and risk factors for VAP in critically-ill patients. Ann Intern Med 1998;129:433-40. This is a well-done, large, multicenter study. Witnessed aspiration, use of paralytics, and underlying medical conditions were among the risk factors identified. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9735080