Postgraduate Course 9 Lower respiratory tract infection … respiratory tract infection in children...

ERS International Congress Amsterdam 2630 September 2015

Postgraduate Course 9 Lower respiratory tract infection in children

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Postgraduate Course 9 Lower respiratory tract infection in children

AIMS: To show how to diagnose and manage common and uncommon lower respiratory tract infections in children. TARGET AUDIENCE: Pulmonologists, respiratory therapists, respiratory physicians, clinical researchers, research fellows, and intensivists.

CHAIRS: J. Grigg (London, United Kingdom), E. Eber (Graz, Austria) COURSE PROGRAMME PAGE

09:30 Evaluation of the child with recurrent chest infections 5 M. Everard (Perth, Australia)

10:15 Management and prevention of non-cystic fibrosis bronchiectasis 54 A. Mller (Zurich, Switzerland)

11:00 Break

11:30 Acute bronchiolitis prevention, diagnosis, and new approaches to management 125

F. Midulla (Rome, Italy)

12:15 Uncommon lower respiratory infections in childhood 170 P. Aurora (London, United Kingdom)

Additional course resources 251

Faculty disclosures 252

Faculty contact information 253

Answers to evaluation questions 254

Edited by Ernst Eber and Fabio Midulla ISBN 978-1-84984-038-5

Th e ERS Handbook of Paediatric Respiratory Medicine comprises more than 100 sections covering the whole spectrum of paediatric respiratory medicine, from anatomy and development to disease, rehabilitation and treatment.

Th e book is structured to tie in with the paediatric HERMES syllabus, making it an essential resource for anyone interested in the fi eld and the ideal training aid for those wishing to take the European Examination in Paediatric Respiratory Medicine.

Accredited by EBAP for 18 hours of European CME credit

To buy printed copies, visit the ERS Bookshop at the ERS International Congress 2015(Hall 1, Stand 1.D_12).

THE ERS HANDBOOK OFpaediatric respiratory medicine

Electronic: WWW.ERSPUBLICATIONS.COMPrint: WWW.ERSBOOKSHOP.COM

www.erspublications.comwww.ersbookshop.com

Evaluation of the child with recurrent chest infections

Prof. Mark L Everard University of Western Australia, Princess Margaret Hospital

Roberts Rd, Subiaco, Perth WA 6008,

Australia [email protected]

SUMMARY In this presentation the diverse causes of chest infections amongst infants and children will be

discussed with a view to developing a systematic approach that can be utilised when faced with a child who has experienced recurrent chest infections. Evaluation of a child who has experienced recurrent chest infections is one of the more common

scenarios facing a respiratory paediatrician in both the outpatient and inpatient settings. The primary challenge is to determine whether child is normal or there is a significant underlying problem that needs to be addressed. Clearly it is important to consider non-infectious causes of recurrent chest infections the commonest scenario being the repeated use of antibiotics to treat children with mild to moderate asthma who experience exacerbations with inter-current viral infections. This is particularly the case in pre-school children in whom both under diagnosis, as above, and over diagnosis [failing to recognise that a child with a viral bronchitis can wheeze without having asthma] are common. More rarely conditions such as idiopathic pulmonary haemorrhage are mis-diagnosed as recurrent severe chest infections due to the extensive CXR consolidation and the associated respiratory viral illness

that frequently triggers the exacerbations. Challenges in infancy and early childhood The majority of those with a significant underlying abnormality such as a significant immunodeficiency, primary ciliary dyskinesia [PCD], cystic fibrosis or significant structural airways problems will start to manifest problems during infancy. However the incidence of significant viral lower respiratory tract infections amongst normal infants and toddlers is higher than at any other time of life with high levels of hospitalisation and significant morbidity. The likelihood of a virus causing significant lower respiratory infections is influenced by both the infecting dose and the pre-existing immunity which is poor in very young subjects once maternally derived antibodies wane. Inevitably many normal children will experience a number of lower respiratory tract infections [LRTIs] (recurrent infections) particularly if they attend a nursery or day-care or have a number of older siblings. Though most acute LRTIs in infancy and early childhood are viral this is also the age at which bacterial pneumonia and invasive pneumococcal disease are at their peak and there no entirely reliable means of distinguishing the viral and bacterial infections. Conversely it is well described that children with disease such as PCD, CF and X-linked agammaglobulinaemia are not diagnosed until well into the first decade of life and hence age of the patient does not preclude the need to consider the more serious and persistent causes Viral-bacterial Interactions It is important to recognise that respiratory viruses can cause a severe life threatening LRTI but also appear to create opportunities for more invasive bacterial organisms to cause lobar pneumonias; trigger exacerbations of a persistent bacterial bronchitis to cause a bronchopneumonia and are the major trigger for exacerbations of asthma which often masquerade as a chest infection. The combination of a runny nose temperature and coughing without obvious wheeze leads many on the

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mailto:[email protected]

mild to moderate end of the asthmatic spectrum to be inappropriately treated with frequent courses of antibiotics and is a common cause for under diagnosis. In these cases the virus is a facilitator of lower airways disease and/or exacerbation rather directly being responsible for the chest infection. Importance of biofilms disease Our relatively recent recognition that bacterial biofilms develop in the lower airway in response to impaired mucocillary clearance provides a conceptual working model for persistent respiratory morbidity and recurrent infections generally triggered by viruses. Our current concepts relating to the development of the radiological appearance bronchiectasis [bronchiectasis is not a disease but a

radiological or pathological appearance the dis-ease is due to the underlying bacterial bronchitis] are based on Prof P. Coles vicious cycle hypothesis in which impaired mucocillary clearance resulting bacterial infection leading to inflammation and damage to the airway resulting in further impairment of mucocillary clearance. Though bronchiectasis can result from certain severe infections such as PVL staphylococcal pneumonia or as part of a condition such as obliterative bronchitis this hypothesis suggests that chronic infection plays a central role and in most cases this is due to impaired mucocillary clearance though in some immune deficiencies permit the colonisation of the airways. Many have had trouble reconciling their understanding that organisms such as Strep. Pneumoniae cause of an acute, but time limited, life threatening pneumonia with the suggestion that the same organism may cause a chronic bacterial bronchitis. However the same individuals recognise the existence of chronic pseudomonal infection of the CF airway and recognise its change of state to a mucoid form represents a much more indolent and difficult to treat state while not understanding the importance of the biofilm. It is now recognised that organisms such as Strep. Pnuemoniae, non-typable haemophilus influenza [NTHi] and Moraxella catarrhalis amongst others are very adept at colonising any niche they can find in the respiratory tract and are associated with chronic otitis media, chronic sinusitis and persistent bacterial bronchitis. The list of conditions predisposing to the establishment of a biofilm is extensive as outlined in table 1. Amongst the causes are conditions known to have poor outcomes unless managed aggressively [such as CF PCD and major immunodeficiencies]. The majority however appear to be due to a self-limiting insult such as an acute viral infection that resolves but leads to on-going morbidity due to the secondary biofilm disease. This may resolve spontaneously in some but equally [depending on extent and management] may progress to severe bronchiectasis over a period time that may range from a months to decades.

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The vicious cycle hypothesis

Biofilm formation and dispersal

Causes of impaired mucocilary clearance

Primary ciliary dyskinesia

Cystic fibrosis

Structural Airways Problems [esp. tracheomalacia +/- bronchomalacia also sig subglottic stenosis, bronchial stenosis etc]

Acute or recurrent aspiration

Impaired coughing [neuromuscular]

Viral LRTI

Post pertussis

Inhaled toxins as in cigarette smoke

Poorly controlled asthma

Foreign Body

Types of chest infections Pneumonia is an infection of the respiratory compartment of the lungs [beyond generation 16] and is characterised by consolidation on a chest x-ray [though the CXR cannot be used to reliably distinguish viral and bacterial disease]. For bacterial infections they are frequently lobar and are caused by organisms such as Strep. Pnuemoniae and HiB the bacteria are planktonic and divide rapidly causing a severe potentially life threatening disease. In general they respond rapidly to antibiotics and it is likely that many cases are treated in primary care without being recognises as pneumonia. Biofilm infections of the conducting airways [generations 1 -16] produce more chronic symptoms with cough predominating. Typically children do not look unwell until they experience and exacerbation generally labelled a chest infection. Any CXR changes are the scruffy, non-specific changes characteristic of peribronchial wall thickening which might be seen in asthmatic subjects, those with a viral infection or PBB. A CXR taken during an exacerbation may capture patchy consolidation of bronchopneumonia [consolidation due to planktonic organisms released by the biofilms in adjacent conducting airways]. Without a clear history seeking evidence of pre-existing or interval cough these exacerbations can be mislabelled as a discrete pneumonias.

Questions to be considered in the evaluation of a child with recurrent chest infections Are these episodes chest infections? Is this asthma triggered by a viral respiratory infection? Is this episodic aspiration without associated infection? Is this a rare episodic problem such as pulmonary haemorrhage masquerading as infection?

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Are the episodes completely discrete with no interval symptoms at all? Makes significant underlying problem less likely Due to the range of viral and bacterial pathogens that are able to cause significant lower

respiratory tract infections Inevitably some children will be experience more than one Does not exclude problems such as intermittent aspiration with subsequent infection, asthma and

some immunological problems Did problems start in early infancy? Increased likelihood of inherited conditions such as PCD & CF; structural airways problems and

aspiration associated with neuromuscular disorders CF but may occur in some normal children. May be associated with some immunological problems though passively derived maternal

antibody provides some protection in antibody deficiencies Many post viral PBB cases start in infancy due to frequency of viral LRTIs.

Are there associated markers of significant underlying disease? failure to thrive with diarrhoea might suggest CF or significant immunodeficiency neonatal respiratory distress and/or significant middle ear problems [PCD] Is there evidence of aspiration with symptoms during and immediately after a feed which may be

due to problems affecting ability to protect airways due to neuromuscular disease and significant cerebral palsy or a structural abnormality such as laryngeal cleft or H-fistula

Has the subject had recent therapy for malignancy with its associated immunosuppression? If imaging has been undertaken are the changes always in the same area? Much less common than variable and multi-lobar May suggest local obstruction such as localised malacia, external compression [vascular, lymph

nodes, malignancy etc.], foreign body etc. Possibly local parenchymal pathology

As with much in respiratory medicine a clear history is the most important component of the assessment focusing on factors such as the age of onset, pattern of symptoms including chronic cough and clues to the presence of an ongoing, underlying cause. Examination is mandatory but can be relatively uninformative. While secretions in the airways may generate harsh inspiratory and expiratory sounds the auscultation is often unhelpful though asking the child to cough, if old enough, is often very valuable. Investigations are driven by the likelihood of finding a significant underlying cause. In some no investigations need be undertaken as they respond well to therapy and the problem resolves. In the face of more persistent /recurrent symptoms or aspects of the history or examination a wide range of investigations maybe undertaken thought there are no studies on which to base recommendations. Bronchoscopy involves and anaesthetic but provides information regarding airways structure

and samples for microbiology. If undertaken all blood samples should be collected at same time. It should be noted that recent courses of antibiotics appear to greatly reduce the chances of culturing bacteria and an interval of 4- 6 weeks is desirable. The presence of significant malacia alter practice in that physiotherapy utilising PEP strategies can be used to help clearance

CT scan can also provide information relating to structure such as airways compression and the presence of bronchiectasis. However the presence of bronchiectasis suggests that there has [in most cases] been inappropriate delay in management. Mild bronchiectasis is reversible with aggressive treatment in the absence of significant underlying pathologies such as CF. It is now possible to obtain CT scans of sufficient quality using a radiation dose of 1 -2 CXR though few centres offer this. Clinicians should be ensuring their radiology Dept. makes this a priority.

Screening for PCD with nasal NO and nasal brushing.

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Immunological screening with antibodies, subclasses vaccine responses, lymphocyte subsets and MBL levels often making up the initial screen. More detailed analysis in conjunction with the immunologists on those with severe progressive disease despite therapy and no other reason for ongoing problems.

In many no specific underlying cause is found and n those with bacterial disease management should be aimed at cure rather than mitigating the rate of progression.

REFERENCES 1. Brand PL, Hoving MF, de Groot EP. Evaluating the child with recurrent lower respiratory tract

infections. Paediatr Respir Rev. 2012;13: 135-8 2. Bush A. Recurrent respiratory infections. Pediatr Clin North Am. 2009; 56: 67-100 3. Chao Y, Marks LR, Pettigrew MM, et al. Streptococcus pneumoniae biofilm formation and

dispersion during colonization and disease. Front Cell Infect Microbiol. 2015; 4:194. 4. Chang AB, Byrnes CA, Everard ML Diagnosing and preventing chronic suppurative lung disease

(CSLD) and bronchiectasis. Pediatr Resp Rev 2011; 12: 97-103 5. Cole PJ. Inflammation: a two-edged sword--the model of bronchiectasis. Eur J Respir Dis Suppl.

1986;147:6-15 6. Couriel J. Assessment of the child with recurrent chest infections. Br Med Bull. 2002; 61: 115-32 7. Craven V, Everard ML. Protracted bacterial bronchitis: reinventing an old disease. Arch Dis

Child. 2013; 98: 72-6 8. Bakaletz LO. Bacterial biofilms in the upper airway - evidence for role in pathology and

implications for treatment of otitis media. Paediatr Respir Rev. 2012; 13: 154-9 9. Everard ML. 'Recurrent lower respiratory tract infections' - going around in circles, respiratory

medicine style. Paediatr Respir Rev. 2012 ; 13: 139-43 10. Hoving MF, Brand PL. Causes of recurrent pneumonia in children in a general hospital. J

Paediatr Child Health. 2013; 49: E208-1 11. Marsh RL, et al. Detection of biofilm in bronchoalveolar lavage from children with non-cystic

fibrosis bronchiectasis. Pediatr Pulmonol. 2014 Mar 18. doi: 10.1002/ppul.23031 12. Reddel H, Ware S, Marks G, Salome C, Jenkins C, Woolcock A. Differences between asthma

exacerbations and poor asthma control. Lancet. 1999; 353: 364-9 13. Rodrigues F, Foster D, Nicoli E et al. Relationships between rhinitis symptoms, respiratory viral

infections and nasopharyngeal colonization with Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus in children attending daycare. Pediatr Infect Dis J. 2013; 32: 227-32

EVALUATION 1. Which of the following are true?

a. Many children with recurrent chest infections do not have a significant identifiable underlying problem

b. It is important to determine whether symptoms entirely resolve between episodes c. Symptoms attributable to recurrent infections may be due to asthmatic exacerbations d. Respiratory viral infections are often responsible for exacerbations of a persistent bacterial

bronchitis leading to a bronchopneumonia e. All children with recurrent chest infections should have a bronchoscopy

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http://www.ncbi.nlm.nih.gov/pubmed/22726867http://www.ncbi.nlm.nih.gov/pubmed/22726867http://www.ncbi.nlm.nih.gov/pubmed/19135582http://www.ncbi.nlm.nih.gov/pubmed/25629011http://www.ncbi.nlm.nih.gov/pubmed/25629011http://www.ncbi.nlm.nih.gov/pubmed/3533593http://www.ncbi.nlm.nih.gov/pubmed/11997302http://www.ncbi.nlm.nih.gov/pubmed/23175647http://www.ncbi.nlm.nih.gov/pubmed/22726871http://www.ncbi.nlm.nih.gov/pubmed/22726871http://www.ncbi.nlm.nih.gov/pubmed/22726868http://www.ncbi.nlm.nih.gov/pubmed/22726868http://www.ncbi.nlm.nih.gov/pubmed/23438187http://www.ncbi.nlm.nih.gov/pubmed/24644254http://www.ncbi.nlm.nih.gov/pubmed/24644254http://www.ncbi.nlm.nih.gov/pubmed/9950442http://www.ncbi.nlm.nih.gov/pubmed/9950442http://www.ncbi.nlm.nih.gov/pubmed/23558321http://www.ncbi.nlm.nih.gov/pubmed/23558321http://www.ncbi.nlm.nih.gov/pubmed/23558321

2. Which of the following are true? a. A clear chest on auscultation excludes significant pathology b. Bronchiectasis indicates that irreversible damage has occurred c. A clear CXR indicates complete resolution of a previous infection d. No growth from a BAL excludes a bacterial infection e. Lipid laden macrophage index is a reliable test for confirming aspiration f. None of the above

3. Which of the following predispose to recurrent chest infections?

a. Attendance at day care b. Previous chemotherapy for malignancy c. diabetes d. Impaired cough e. Laryngeal cleft

4. Which of the following are true of respiratory viral infections?

a. They may precede the development of a persistent bacterial bronchitis b. The may precede the development of an acute bacterial lobar pneumonia c. They may trigger an exacerbation of asthma d. They may be detected in asymptomatic individuals e. The severity of a viral cold is influenced by the load of potentially pathogenic bacteria in the

upper airway

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Mark L. Everard

University of Western Australia, Princess Margaret Hospital

Evaluation of the child with recurrent chest infections

When I use a word, Humpty Dumpty said in a rather scornful tone, it means just what I choose it to mean, neither more nor less

Lewis Carrol Through the Looking-Glass 1872

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http://www.uwa.edu.au/university-campaigns-resources/emailsig-resources/uwa-logo/http://www.uwa.edu.au/university-campaigns-resources/emailsig-resources/uwa-logo/

Conflict of interest disclosure

I have no, real or perceived, direct or indirect conflicts of interest that relate to this presentation.

This event is accredited for CME credits by EBAP and speakers are required to disclose their potential conflict ofinterest going back 3 years prior to this presentation. The intent of this disclosure is not to prevent a speaker with aconflict of interest (any significant financial relationship a speaker has with manufacturers or providers of anycommercial products or services relevant to the talk) from making a presentation, but rather to provide listeners withinformation on which they can make their own judgment. It remains for audience members to determine whether thespeakers interests or relationships may influence the presentation.Drug or device advertisement is strictly forbidden.

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Chest Infection

Ceftriaxone

CRP 385

What type of chest infection?

Lobar pneumonia?

Bronchopneumonia?

Pneumococcal pneumonia?

Viral pneumonia?

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5 years old Chronic cough from 10 months of age 1 previous admission with pneumonia Thriving

Possible underlying causes?Asthma

BronchiectasisPost viral persistent bacterial bronchitis

Inhaled foreign bodyCystic fibrosis

AgammaglobulinaemiaAspirationBad luck

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12 years old - referred by practice nurseFrequent abs as infant

Eczema as infant - mother with eczema as childAsthma at 4 yrs of age

Seretide 250 bd singulair 5mgsRecent pneumonia

FEV1 99%Did not appear unwell

Difficult asthma Do recurrent chest infections have a role?

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12 years old - referred by practice nurseFrequent abs as infant

Eczema as infant - mother with eczema as childAsthma at 4 yrs of age

Seretide 250 bd singulair 5mgsRecent pneumonia

FEV1 99%

Symptom free within 2 years off all medication

Difficult asthma or recurrent chest infections?

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Chest InfectionsConducting vs Respiratory Airways

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Bacterial Bronchitis Vs Pneumonia

CRP 326

Bjarnsholt 09

18

Koch's postulates :

The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms.

The microorganism must be isolated from a diseased organism and grown in pure culture.

The cultured microorganism should cause disease when introduced into a healthy organism.

The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

a long, long time ago

* 1890 to be precise

*

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Pneumoniarespiratory disease characterized by inflammation of the lung parenchyma (excluding the bronchi) with congestion caused by viruses or bacteria or irritants

Congestion

Red hepatization

Gray hepatization

Resolution

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How is pneumonia diagnosed?

WHO

history of cough and/or difficulty breathing ( 2 months > 60/min 2-11 months > 50/min > 11 months > 40/min

Cherian et al Bull WHO. 2005;83(5):353359

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How is it diagnosed?

UK Bacterial pneumonia should be considered in children aged up to 3

years when there is fever of >38.5C together with chest recession and a respiratory rate of >50/min.

For older children a history of difficulty in breathing is more helpful than clinical signs.

Chest radiography should not be performed routinely in children with mild uncomplicated acute lower respiratory tract infection

Radiographic findings are poor indicators of aetiology.

BTS UK Community acquired pneumonia guidelines 22

Consolidation and LRTIs

The Gambia: 16.7% of 3,941 LRTI episodes had CXR-AC.

South Africa (HIV-): 19.2% of 1,106 LRTI episodes had CXR-AC

Phillipines: 13.8% of hospital pneumonia and 5.9% of OP pneumonia.

USA: 12% of pneumonia episodes had CXR-AC

Fiji: 34% of 174 LRTI episodes had CXR-AC.

Enwere G et al. Trop Med Int Health Nov 2007; 12; Madhi SA et al. Clin Infect Dis; 2005: 40; Lucero et al. Pediatr Infect Dis J 2009;28: 455462, Magree HC et al. Bull Wld Health Org; 2005; 83. 23

Aetiology of pneumonia

Streptococcus pneumoniae 35.7% 7.3% 7.8%

Haemophilus influenzae 26.1% 0.6%

Mycoplasma pneumoniae 17.8% 3.7% 15.7%

Group A Streptococcus 3.2%

Staph aureus 1.3%

Pertussis 0.3% 6.7%

Chlamydia 1.1%

Viruses 17.8% 12.7% 25.8%

Unknown 19.7% 71% 35%

Tokyo NE England Nottingham

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Non-CF Bronchiectasis

25

Bronchiectasis is a radiological or pathological description

The dis-ease is the bacterial bronchitis

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BronchiectasisVicious Circle Hypothesis

Inflammation

Airways damage

Impaired mucocillary clearance

Infection

PBB - Bronchiectasis Vs IHD MI27

Biofilmsbacterial population(s), encased in an auto-produced matrix

[EPS], which may contain host components, adhering with each other and/or to a surface

extracellular polymeric substances [EPS] polysaccarides, proteins, alginates, eDNA, lipids, collagen etc

NTHi otitis media: ds DNA + piliBakaletz et al

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Benefits of biofilm formationBacteria within a biofilm are protected by multilayered defences both physical and biological

Can co-ordinate response to host, physical environment and other micro-organisms

Highly organised communitiesOptimise to nutrient availability and other stresses

Reduced growth rate - low metabolic rate

Different transcriptome switch on and off virulence factors etcExchange genetic information more frequently

Share enzymesPhysical barrier to host cells, antibodies and removal

Sig increase in antibiotic resistance [upto 1000X]

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Biofilm maturationSurface attachment

Microcolony formation

Dispersal

99.9% of total world bacterial biomass exists in biofilms!

Bakaletz L et al 2011

planktonic cells

Quorum Sensing

Process may occur without any clinical signs or symptoms

Chatorajj Thorax 2011

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Bacteria have been using extracellular polymeric substances (EPS) to create their own protected microenvironment for >3.5 billion yrs

Noffke et al 2013

EPS = slime

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Controls BronchiectasisID 9 10 11 1 2 3 4 5 6 7 8Biofilm Lavage 1 - - - - - + - + - - +Biofilm Lavage 2 - - - + - + + + + + +

BALs of children with non-CF bronchiectasis & PBB

Marsh, Thornton, Chang et al, Pediatric Pulmonology, 2014

WGA and Con A

32

Koch's postulates :

The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms.

The microorganism must be isolated from a diseased organism and grown in pure culture.

The cultured microorganism should cause disease when introduced into a healthy organism.

The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

a long, long time ago*

33

PCV Reduces The Incidence Of Hospitalization for Viral-Associated Pneumonia In Children

Virus PCV Placebo Efficacy 95%C.I. P value

Influenza A/B 31 56 45 14 to 64 0.01

PIV 1-3 24 43 44 8 to 66 0.02

hMPV 26 62 58 34 to 73 0.001

RSV 90 115 22 -3 to 41 0.08

Madhi SA & Klugman KP. Nature Med.2004. 10: 811-813;Madhi SA et al. J Infect Dis 2006; 193:1236-43

At least one-third of placebo-recipients hospitalized for pneumonia in whom a virus was identified had concurrent infection due to VT pneumococcus

Viral infections and IPD

Bacterial - Viral Interactions

Chattoraj et al 2011

PsA HRV NADPH oxidase34

Rodrigues 2010 Ped Inf Dis J

SNOT - Virus and Bacteria

35

Aetiology of persistent infection and associated chest infections

Inflammation

Airways damage


InfectionViral LRTITracheobronchomalaciaAsthmaAspirationCFPertussisPCDCP/neuromuscularSmokingetc

ImmunodeficiencyEsp antibidody

PBB - Bronchiectasis Vs IHD MI36

History & Investigations[see abstract]

Response to appropriate treatment assessed at appropriate time

? Bronchoscopy

?CT

[ensure minimum dose is used]

?Immunological investigations

?videofluroscopy/oesophograms etc

Cilial function/CF genetics/sweat test37

Regression to the mean and tuning out

Hes a new boy

Hes sleeping better and not coughing as much

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Marchant J M et al. Chest 2008;134:303-309

Impact on Quality of Life

Petsky HL J Pediatr Child Health 2010

Its just another virusTry this inhaler

You are the first Dr to listen to me

Morbidity Regression to the mean

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Diagnosis of Biofilm Disease?

NTHi 3.5 X 103 CFU/mL Strep P 4 X 103 CFU/mL Moraxella ++

Pt 1

Pt 2

When bacteria are in the biofilm phenotype they are unlikely to be in a cultureable state and thus PCR maybe needed for detection

1 > 10 ?4

41

Diagnosis of Biofilm Disease?

NTHi 3.5 X 103 CFU/mL Strep P 4 X 103 CFU/mL Moraxella ++

Pt 1

Pt 2

Quantitative versus qualitative cultures of respiratory secretions for clinical outcomes in patients with ventilator associated pneumonia

There is no evidence that the use of quantitative cultures of respiratory secretions results in reduced mortality, reduced time in ICU and on mechanical ventilation, or higher rates of antibiotic change when compared to qualitative cultures in patients with VAP.

When bacteria are in the biofilm phenotype they are unlikely to be in a cultureable state and thus PCR maybe needed for detection

1 > 10 ?4

42

Same Sample Different Resut

43

Treatment Evidence Free Zone

Inflammation

Airways damage


Infection

AntibioticsOral

Inhaled IVs

PhysiotherapyPEP when appropriate

? hypertonic saline

?? macrolides

*** Deal with initiating problem if still present ***

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Treatment?[not prophylaxis]

Treat with antibiotics until cough resolves [Phelan]

Cough takes 10 -14 days to clear with high dose antibiotics

? Long courses to allow airways to repair

? side effects

? compliance

? resistance

Coughing implies inflammation and healing will not take place

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A B

Treat the bacterial bronchitis and the radiological bronchiectasis can resolve at least if treated early enough

Bronchiectasis usual represents medical neglect 46

1980s

under diagnosis of asthma in 7 yr olds

Doctors are fearful of using the term asthma

All too often the (viral) bronchitis is treated with antibiotics while the wheeze is ignored

Recent research has undermined this belief [wheezy bronchitis is a separate clinical entity] and there is little clinical value in distinguishing them since the treatment is the same

96% identified by the single question has your child ever had attacks of wheezing?

Speight ANP BMJ 198347

Diagnosis? 7 yrs old with chestiness in winter

Some response to ventolin

?asthma

48

PMNs

Heavy growth of H Inf

49

Persistent endobronchial infection with bronchopneumoniaexacerbation of PBB

biofilm and planktonic disease

BAL Left Lower Lobe Heavy growth of NTHi PMNs +++50

Amanda age 6 years. One of 5 children - asthma diagnosed at age of 2.5 yrs and treated initially with agonist alone. Older brother has asthma but grew out of it before he went to school. Subsequently started on ICS and last year commenced LABA.

Currently symptomatic with cough particularly at night, first thing in the morning and with exercise.

Several pets, both parents smoke and are unemployed. Has had many courses of antibiotics for chest infections

and is frequently prescribed antibiotics at the same time as oral steroids which usually helps for a while but symptoms soon return.

What is the likely problem and what would you do?51

April is 3 yrs of age - had many courses of antibiotics for ear and chest infections during the past 2 years.

No family history of asthma, eczema when a baby. Lives in 2 bedroom council flat with mother and 3 siblings. Generally well though is very tired and crabby particularly with chest

infections and looses appetite. Main problem is cough, possibly wheezed during an earlier chest

infection. Always has loose stools and is still in nappies. 1 cat, mother does not smoke. Mother has applied for re-housing because of the damp bedrooms

and Aprils chest problems.

What is the likely problem and what would you do?52

The importance of a persistent bacterial bronchitis in recurrent chest infections

Diagnosis can be difficult, mis-diagnosis is common both under and over

A persistent bacterial bronchitis [biofilm] causes the dis-ease Relatively common Cause of significant morbidity Bronchiectasis is a largely preventable radiological appearance

? Place for bronchoscopy

? Place for CT

? Optimal therapy 53

Management and prevention of non-cystic fibrosis bronchiectasis

Dr Alexander Moeller Head Division Respiratory Medicine University Children's Hospital Zurich

Steinwiesstrasse 75 8032 Zurich

SWITZERLAND [email protected]

SUMMARY Bronchiectasis in children without cystic fibrosis (non-CF bronchiectasis) is a morphological term describing abnormal, irreversibly dilated and often thick-walled bronchi [1,2] and is believed to be the end result of chronic or repeated episodes of environmental insults. The pathophysiology is not yet completely understood, however it is very likely that airway damage is caused by inflammation and bacterial infection superimposed on a background of genetic vulnerability [1]. Bronchiectasis is associated with frequent bacterial infections and inflammatory destruction of the bronchial and peri-bronchial tree. Whilst originally described in histopathological terms bronchiectasis is defined radiologically in clinics [2]. Bronchiectasis is thought to be the end result of suppurative lung disease and a consequence of persistent airway bacterial colonization. [3] More than 60% of children with bronchiectasis have an underlying disorder. In a systematic review including a total of 989 children with bronchiectasis infectious (17%), primary immunodeficiency (16%), aspiration (10%), ciliary dyskinesia (9%), congenital malformation (3%), and secondary immunodeficiency (3%) were the most common disease categories, whereas severe pneumonia of bacterial or viral aetiology and B cell defects were the most common disorders identified. [4] Reduced mucociliary clearance is the consequence of different basic disorders and results in mucostasis associated with airway colonisation and finally chronic infection with mucoid transformation and biofilm production. The neutrophil mediated inflammation together with the release of proteolytic enzymes results in airway and tissue injury leading to further reduction of mucociliary clearance. [1] Chronic wet cough is the most important symptom leading to the suspicion of suppuratives lung disease and bronchiectasis in a child. [5] Both protracted bacterial bronchitis and failed chronic wet cough response to antibiotics are predictors of bronchiectasis [5, 6].

54

Table 1. Symptoms / Signs Wet cough Daily sputum production Hemoptysis Pleuritic chest pain Pulmonary osteoarthropathy Delayed growth When to suspect bronchiectasis Chronic moist/productive cough Asthma that does not respond to treatment Incomplete resolution of a severe pneumonia, or recurrent pneumonia Pertussis-like illness failing to resolve after six months Persistent and unexplained physical signs, i.e. persistent lung crackles Respiratory symptoms in children with structural or functional disorders of the oesophagus and

upper respiratory tract Unexplained haemoptysis If bronchiectasis is suspected based on the history, clinical signs and or chest radiography a high-resolution CT scan should be performed when possible in inspiration to rule out or confirm the presence of bronchiectasis. [2,7,8] The key features of bronchiectasis on HRCT scans are (a) one or more dilated bronchi defined as the internal luminal diameters of the airways exceeding the diameter

of the adjacent vessel, (b) non-tapering of the bronchi, (c) presence of visible bronchi adjacent to the mediastinal pleura or within the outer 1- 2 cm of the lung fields. If bronchiectasis is confirmed in a child, the following diagnostic steps should be performed (Table 2). Table 2: further diagnostics modified from [9] Sweat test Mandatory to rule out cystic fibrosis Test of immune function Serum immuno-globulins

IgG-subclasses Specific antibodies to vaccinations

Pertussis, diphtheria, tetanus toxoid, capsular polysaccharides of Streptococcus pneumoniae and Haemophilus influenzae type B

Repeat 4 weeks after vaccination-boost if low Lymphocyte B and T cell subsets Mantoux and others HIV

Testing for PCD Step-wise approach [10]

Nasal nitric oxide Nasal brushing High frequency video microscopy analysis (HVMA) Transition-electron microscopy Immune-fluorescent microscopy Genetics

Test for pulmonary aspiration Primary and secondary aspirations, children with neurological disorders Bronchoscopy Not mandatory, may give information on non-sputum producing children

55

Bronchiectasis is associated with significantly lower child-rated physical health quality of life (QOL) scores [11, 12] and lower sleep quality [13]. Wheezing and dyspnoea severity, number of exacerbations and frequency of antibiotic requirements were all associated with lower QOL [11, 12]. Regular microbiological investigations are a cornerstone of the management of non-CF-bronchiectasis. A broad range of airway pathogens are regularly found in children with bronchiectasis including Haemophilus influenza, Streptococcus pneumonia, Moraxella catarrhalis, Pseudomonas aeruginosa, Staphylococcus aureus, and Aspergillus species. [15, 16, 17]. The implementation of preventive measures has the potential to reduce the risk of development and the progression of bronchiectasis [18]. In addition appropriate treatment reduces exacerbations of bronchiectasis and prevents deterioration of lung function [14, 16, 19]. Some children may need prolonged antibiotic treatment, whenever possible according to microbiology. Airway damage can be limited by intensive treatment, even in those predestined to have bronchiectasis. [20, 21] Table 3: Preventive measures modified from [21]

Primary prevention Secondary prevention Tertiary prevention

Normal lung development Early detection Reduce morbidity, mortality and secondary complications

Removal of modifiable risk factors

Appropriate treatment Reduce adverse events from medication

ARIs, CSLD, Bronchiectasis

Environmental health (hygiene, sanitation, pollution)

Good follow up of all acute respiratory episodes

Assessment for treatable causes

Identification of predispositions to recurrent ARIs and CSLD

Early diagnosis of bronchiectasis

Prevent exacerbations trough optimization of treatment

Early treatment of exacerbations

Asthma Obtain good asthma control

Mainstays of treatment 1. Airway clearance techniques. These are similar to the techniques used in the management of

cystic fibrosis and include oscillatory positive expiratory pressure devices (PEP), selective breathing and chest physiotherapy. [9]

2. Aerosol therapy including hyperosmolar agents such as hypertonic saline and mannitol. Bronchodilators are frequently prescribed without clear evidence. [9,22]

3. Antibiotics are used to either treat exacerbations in an empiric manner or guided by microbiology or intermittently to reduce bacterial load. Long-term treatment with azithromycin has been evaluated in different studies including children with bronchiectasis or chronic suppurative lung disease. Whereas there was a clear reduction in the number of exacerbations, there was a

56

significant increase in azithromycin-resistant airway pathogens. [24, 25]. A recent meta-analysis did not reveal a significant effect on lung function by long-term macrolide treatment. [25]

4. Regular exercise is an important treatment option. 5. Surgery is rarely indicated and performed only in localised disease in the case of significant

symptoms unable to be controlled by medical therapy or for the treatment of complications such as empyema, recurrent haemoptysis, lung abscess.

6. Vaccinations, including annual influenza vaccination and 5-yearly Pneumococal vaccination are considered an important preventive measure. [26,27]

REFERENCES 1. Cole PJ. Inflammation: a two edged sword the model of bronchiectasis. Eur. J. Respir. Dis.

Suppl. 1986; 147: 615. 2. Eastham KM, Fall KJ, Mitchell L, Spencer DA. The need to redefine non-cystic fibrosis

bronchiectasis in childhood. Thorax 2004; 59: 3247. 3. Chang AB, Redding GJ, Everard ML. State of the Art - Chronic wet cough: protracted bronchitis,

chronic suppurative lung disease and bronchiectasis. Pediatr Pulmonol 2008;43:51931 4. Brower, K. S., Del Vecchio, M. T., & Aronoff, S. C. The etiologies of non-CF bronchiectasis in

childhood: a systematic review of 989 subjects. BMC Pediatrics, 2014, 14(1), 299. 5. Chang, A. B., Robertson, C. F., Asperen, P. P. Van, Glasgow, N. J., Mellis, C. M., Masters, I. B.,

Landau, L. I. A Multicenter Study on Chronic Cough, CHEST 2015; 943950. 6. Goyal, V., Grimwood, K., Marchant, J., Masters, I. B., & Chang, A. B. Does failed chronic wet

cough response to antibiotics predict bronchiectasis? Archives of Disease in Childhood, 2014; 99(6), 5225.

7. Li, a. M., Sonnappa, S., Lex, C., Wong, E., Zacharasiewicz, a., Bush, a., & Jaffe, a. Non-CF bronchiectasis: Does knowing the aetiology lead to changes in management? European Respiratory Journal 2005; 26(1), 814.

8. Chang AB, Masel JP, Boyce NC, Wheaton G, Torzillo PJ. Non-CF bronchiectasis clinical and HRCT evaluation. Pediatr. Pulmonol. 2003; 35: 47783.

9. Lucas JS, Burgess A, Mitchison HM, et al. Diagnosis and management of primary ciliary dyskinesia. Arch Dis Child 2014; 99:850856.

10. Bahali, K., D, M., Gedik, A. H., D, M., Bilgic, A., D, M., (2014). The relationship between psychological symptoms , lung function and quality of life in children and adolescents with non-cystic fibrosis bronchiectasis General Hospital Psychiatry 2014; 36: 528532

11. Gokdemir, Y., Hamzah, A., Erdem, E., Cimsit, C., Ersu, R., Karakoc, F., & Karadag, B. Quality of Life in Children with Non-Cystic-Fibrosis Bronchiectasis. Respiration, 2014; 88(1), 4651.

12. Erdem, E., Ersu, R., Karadag, B., Karakoc, F., Gokdemir, Y., Ay, P. Dagli, E. Effect of night symptoms and disease severity on subjective sleep quality in children with non-cystic-fibrosis bronchiectasis. Pediatric Pulmonology, 2011; 46(9), 919926.

13. Bastardo, C. M., Sonnappa, S., Stanojevic, S., Navarro, a, Lopez, P. M., Jaffe, Bush A. Non-cystic fibrosis bronchiectasis in childhood: longitudinal growth and lung function. Thorax 2009, 64(3), 246251.

14. Grimwood, K. Airway microbiology and host defences in paediatric non-CF bronchiectasis. Paediatric Respiratory Reviews 2011; 12(2), 111118.

15. Kapur, N., Grimwood, K., Masters, I. B., Morris, P. S., & Chang, A. B. Lower airway microbiology and cellularity in children with newly diagnosed non-CF bronchiectasis. Pediatric Pulmonology, 2012, 47(3), 300307.

16. Tunney, M. M., Einarsson, G. G., Wei, L., Drain, M., Klem, E. R., Cardwell, C.; Elborn, J. S. Lung microbiota and bacterial abundance in patients with bronchiectasis when clinically stable and during exacerbation. American Journal of Respiratory and Critical Care Medicine, 2013, 187(10), 11181126.

17. Chang, A. B., Byrnes, C. a., & Everard, M. L. (2011). Diagnosing and preventing chronic suppurative lung disease (CSLD) and bronchiectasis. Paediatric Respiratory Reviews, 2011; 12(2), 97103.

57

18. Chang, A. B., Robertson, C. F., van Asperen, P. P., Glasgow, N. J., Masters, I. B., Teoh, L.,Morris, P. S. A cough algorithm for chronic cough in children: a multicenter, randomized controlled study. Pediatrics, 2013; 131(5), e157683.

19. Chang, A. B., Brown, N., Toombs, M., Marsh, R. L., & Redding, G. J. (2014). Lung disease in indigenous children, Paediatric Respiratory Reviews 15 (2014) 325332

20. Rubin BK. Overview of cystic fibrosis and non-CF bronchiectasis. Semin. Respir. Crit. Care Med. 2003; 24: 61927.

21. Rubin BK. Aerosolized antibiotics for non-cystic fibrosis bronchiectasis. J. Aerosol Med. 2008; 21: 16.

22. Valery, P. C., Morris, P. S., Byrnes, C. a., Grimwood, K., Torzillo, P. J., Bauert, P. ;Chang, A. B. Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study): A multicentre, double-blind, randomised controlled trial. The Lancet Respiratory Medicine, 2013, 1(8), 610620.

23. Gao, Y. H., Guan, W. J., Xu, G., Tang, Y., Gao, Y., Lin, Z. Y.,Chen, R. C. Macrolide therapy in adults and children with non-cystic fibrosis bronchiectasis: A systematic review and meta-analysis. PLoS ONE, 2014; 9(3).

24. Haciibrahimoglu G, Fazlioglu M, Olcmen A et al. Surgical management of childhood bronchiectasis due to infectious diseases. J. Thorac. Cardiovasc. Surg. 2004; 127: 13615.

25. Sirmali M, Karasu S, Turut H et al. Surgical management of bronchiectasis in childhood. Eur. J. Cardiothorac. Surg. 2007; 31: 1203

EVALUATION A 6 years old non-allergic boy is referred because of chronic cough since more than 2 years. As he was coughing more during exercise the GP has initiated an inhalation therapy including salbutamol and fluticasone proprionate, however without persistent improvement. At birth he was tachypnoeic and needed some oxygen for wet-lungs. In addition he suffers from a runny nose all year 3 episodes of otitis media. He had recurrent chest infections in the past and several courses of short-time (3-5 days) oral antibiotics in the past with a good clinical response but a relapse of cough after some weeks. A chest radiograph showed situs inversus, some pronounced peribroncho-vascular structures and non-specific bronchial thickening in both lower lobes and atelectasis of the middle lobe. You have the suspicion of bronchiectasis. 1. Which diagnostic investigation do you perform first:

a. Bronchoscopy and bronchoalveolar lavage b. HRCT-scan of the lung c. Sweat test d. Immunological-work up

2. What are the most common underlying diseases or aetiologies associated with non-cf-

bronchiectasis in children? a. lung infections b. primary immunodeficiency c. aspiration d. ciliary dyskinesia e. congenital malformation f. all of above

3. Which is the most likely underlying disease of this boy?

a. Cystic fibrosis b. B-cell immunodeficiency c. Primary ciliary dyskinesia d. Congenital pulmonary airway malformation

58

4. As there is a chronic atelectasis of the middle lobe surgery should be taken into

consideration. a. Yes, this is a source of recurrent infection, the middle lobe should be excised. b. No, surgery is never indicated in this situation c. The excision should not be limited to the middle lobe, as also the lower lobe shows

severe bronchiectasis. d. Surgery is indicated for the treatment of complications such as empyema, recurrent

haemoptysis, lung abscess

5. As most of children with non-cf-bronchiectasis have chronic airway colonization and infection antibiotic therapy is a mainstay of the management. Which of the following statements are correct

a. Long-term therapy with azithromycin results in significant reductions of exacerbations and improvement in lung function

b. Whenever possible antibiotic therapy should be based on bacteriology results c. Long-term inhaled antibiotics such as tobramycin is associated with a significant

clinical improvement d. Exacerbations should always be treated with intravenous antibiotics

59

Management and prevention of non-cystic fibrosisbronchiectasis

PD Dr. med. Alexander MoellerHead Division Respiratory Medicine

Pediatric pulmonology

60

2

Consultant for Novartis, Vertex and Gilead

Grant support: Zurich lung league

STARR-Foundation

No real or perceived conflicts of interest that relate to this presentation

Disclosure

61

Non-CF bronchiectasis

the end result of chronic or repeated episodes of environmental insults

superimposed on a background of genetic vulnerability (?)

Sixty-three percent of the subjects had an underlying disorder

Spectrum related to airway bacteria

Associated degradation and inflammation products causing airway damage

Cole P. Eur J Respir Dis Suppl 1986;147:6:15

62

Definition

Morphological term: abnormal irreversibly dilated and often thick-walled bronchi

Frequent bacterial infections

Inflammatory destruction of the bronchial and the peri-bronchial tree

End result of suppurative lung disease

Radiological definition for a histo-pathological problem

Eastham KM. Thorax 2004; 59: 3247

63

Bronchiectasis as part of spectrum of suppurative lung disease

Chang AB. Pediatr Pulmonol 2008;43:519-31

Protracted bacterial bronchitis

Chronic suppurative lung disease

Bronch-iectasis

Progression of clinical severity

64

Pathophysiology

Airway injury

Reduced mucociliary

clearance and recurrent or

chronic lower airway infection

Neutrophil mediated

inflammation

Proteolyticenzymes

65

Symptoms / sputum

Chronic bacterialinfection

Transient colonisation

Free of infection

Mucostasis

Mucociliary Clearance

Pathogenesis

Chronic inflammation

Mucostasis

Insult Insult Insult Insult

Mucoid /biofilmbacterial infection

pertussismeasles adenovirus tuberculosis

66

Effective airway-clearance

Airway-clearance

Ciliary function Cough function

Mucus rheologyLung function

Fluss(l/s)

Volumen (l)

PEFMEF75

MEF50

MEF25

Exspiration

Inspiration

50 25 0%75100

67

Ineffective airway-clearance

CF / Bronchitis

PCDNMD

Airway-obstruction

Recurrentinfections

68

Non-CF bronchiectasis Pathophysiology

Cole P. Eur J Respir Dis Suppl 1986;147:6:15

Impaired host

defence

Bacterial colonisation

Biofilm formation

Chronic inflammation

Airway / tissue

damage

Reduction of

mucociliaryclearance

Underlying disorder

Healthy child

Genetic suscept-

ibility

Environ-mental insult

69

Associations with non-CF bronchiectasis

Association Total number % of total

No association 308 34%

Infectious 174 19%

Primary immunodeficiency 158 17%

Aspiration/foreign body 91 10%

Primary ciliary dyskinesia 66 7%

Congenital malformation 34 4%

Secondary immunodeficiency 29 3%

Asthma 16 2%

Bronchiolitis obliterans 12 1%

Skeletal diseases Others 11 1%

Others 7 1%

Brower KS. BMC Pediatrics 2014, 14:29970

Congenital malformations associated with non-CF bronchiectasis

Malformation n=27 Total number % of total

Tracheo-oesophageal fistula 14 52%

Cystic lung disease 5 19%

Bronchogenic cyst 2 7%

Yellow nail syndrome 1 4%

Tracheomalacia 1 4%

Congenital lobar emphysema 1 4%

Pulmonary artery sling 1 4%

Bronchial atresia 1 4%

Bronchomalacia 1 4%


71

Infectious diseases associated with non-CF bronchiectasis

n = 108 Total number % of total

Pneumonia* 66 61%

Measles 15 14%

Tuberculosis 12 11%

Interstitial pneumonia 3 3%

Varicella 3 3%

Neonatal pneumonia 1 1%

Allergic bronchopulmonary aspergillosis (ABPA)

2 2%

Pertussis 5 5%

Adenovirus 1 1%

Severe viral or bacterial pneumonia. *Pneumonia at age 6 months or less


72

Primary immunodeficiencies associated with non-CF bronchiectasis

Total number % of total

B cell disorders 97 74%

IgG deficiency* 63 48%

IgG subclass deficienca 24 18%

IgA deficiency 9 7%

B cell deficiency NOS 1 1%

T cell disorders 9 7%

Hyper IgE syndrome 3 2%

Hyper IgM syndrome 2 2%

T cell deficiency 3 2%

Chronic mucocutaneous candidiasis 1 1%

common variable immunodeficiency (30), IgG deficiency (13), agammaglobulinemia (10) andantibody deficiency or dysfunction


73

Primary immunodeficiencies associated with non-CF bronchiectasiscont

Total number % of total

Combined immunodeficiency 13 10%

Severe combined immunodeficiency 9 7%

Ataxia-telangiectasia 2 2%

Wiskott-Aldrich syndrome 2 2%

Chronic granulomatous disease 7 5%

Barre lymphocyte syndrome/MHC class II deficiency

2 2%

Mannose-binding protein deficiency 1 1%

Other disorders 2 2%


74

Chang A. CHEST 2012; 142(4):943950

Protracted bacterial bronchitis: a predictor of bronchiectasis

346 children (mean age 4.5 years) newly referred with chronic cough >.4 weeks)

75

Chang A. CHEST 2012; 142(4):943950


346 children (mean age 4.5 years) newly referred with chronic cough >.4 weeks)

76

Chang A. CHEST 2012; 142(4):943950


77

Failed chronic wet cough response to antibiotics andbronchiectasis

Goyal V. Arch Dis Child 2014;99:522525

78

Suspecting the diagnosis

chronic moist/productive cough,

especially between viral colds and lasting 8 weeks

Asthma that does not respond to treatment

Incomplete resolution of a severe pneumonia, or recurrent pneumonia

Pertussis-like illness failing to resolve after six months

Persistent and unexplained physical signs, i.e. persistent lung crackles

Respiratory symptoms in children with structural or functional disorders of the oesophagus and upper respiratory tract

Unexplained haemoptysis.

79

Symptoms

Indolent onset chronic respiratory symptoms

Cough Daily sputum production

may be present for years before diagnosis

Hemoptysis pleuritic chest pain pulmonary osteoarthropathy delayed growth

80

Diagnosis

1. Radiologic imaging2. Sweat test3. Test of immune function4. Testing for PCD5. Test for pulmonary aspiration6. Bronchoscopy (?)

81

Diagnosis1. Radiologic imaging

Chest radiograph Insensitive If normal Bx not excluded Poor correlation to HRCT

High-resolution CT scan Inspiration Distribution of Bx not correlated

to underlying disease

Eastham KM. Thorax 2004; 59: 3247Chang AB. Pediatr. Pulmonol. 2003; 35: 47783

Li AM. Eur. Respir. J. 2005; 26: 814 82

The key features of bronchiectasis on HRCT scans (a) one or more dilated bronchi

defined as the internal luminal diameters of the airways exceeding the diameter of the adjacent vessel,

(b) non-tapering of the bronchi (c) presence of visible bronchi

adjacent to the mediastinalpleura or within the outer 1- 2 cm of the lung fields.


83


84


85

Diagnosis2. Sweat test

Mandatory (caveat: newborns screening) Experienced laboratory May be repeated if non- conclusive

86

Diagnosis3. Test of immune function

Serum immuno-globulins IgG-subclasses Specific antibodies to vaccinations

Pertussis, diphtheria, tetanus toxoid, capsular polysaccharides of streptococcus pneumoniae and Hameophilus influenzae type B

Repeat 4 weeks after vaccination-boost if low Lymphocyte B and T cell subsets Mantoux and others HIV

87

Diagnosis4. Testing for Primary Ciliary Dyskinesia

88

Diagnosis4. Testing for Primary Ciliary Dyskinesia

Nasal nitric oxide

Karadag, Eur Respir J 1999

89

Diagnosis4. Testing for PCD

Nasal nitric oxide Nasal brushing High frequency video

microscopy analysis (HVMA)

normal

immotile

dyskinetic

Circulardyskinesia

90



microscopy analysis (HVMA) Transition-electron microscopy

91



microscopy analysis (HVMA) Transition-electron microscopy Immune-fluorescent microscopy

Omran et al., Am J Hum Genet 2008

92

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668028/figure/fig4/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668028/figure/fig4/



microscopy analysis (HVMA) Transition-electron microscopy Immune-fluorescent microscopy Genetics

93

Aspirations

primary

Secondary

Children with neurologic disease

Diagnosis5. Pulmonary aspiration

94

Aspirations

primary

Secondary



95

Aspirations

primary

Secondary



96

Aspirations

primary

Secondary



97

ManagementQuality of life

significantly lower child-rated physical health QOL scores all of the parent-rated QOL scores significantly lower

Variables associated with lower QOL: Wheezing severity*

Dyspnoea severity*

Number of exacerbations*

Pulmonary function**

Frequent antibiotic requirement**

Not with CT scores**

Bahali K. General Hosp Psychiatry 2014;36: 528532Gokdemir Y. Respiration 2014;88:4651

* Pediatric Quality of Life Inventory Child/Parent Version (PedsQL-P)** St. Georges Respiratory Questionnaire (SGRQ)

QOL in Children with Bronchiectasis Respiration 2014;88:4651 DOI: 10.1159/000360297

49

Discussion

To our knowledge, this is the first study evaluating the HRQOL of children with non-CF BE in which the ques-tionnaires were completed by the children. We evaluated HRQOL in non-CF BE children and also assessed the ef-fects of clinical characteristics and SES from generic (SF-36) and disease-specific (SGRQ) QOL questionnaires. The SGRQ symptoms score was better in patients with longer, regular follow-up periods, and patients with low PFT values had worse symptoms scores. Patients with a low SES were diagnosed later than those with a higher SES.

One important limitation of this study was that the SGRQ and SF-36 questionnaires have not been validated in children. They have been previously used for children (612 years of age), however [17, 18] .

Although several QOL scales have been developed for chronic respiratory diseases (asthma, COPD and cystic fibrosis), there is no specific QOL scale for non-CF BE [12] . Generic and specific (CF or adult chronic lung disease) scales have been used to determine the QOL with non-CF BE adult patients. Studies have shown that HRQOL has been adversely affected in adults with non-CF BE [9, 1216] . The SGRQ is the only scale that measures disease-specific QOL in adult pa-tients which has been used in a few studies in non-CF BE [9, 1214] . Although the SGRQ and the SF-36 have been used for children (612 years) previously, they were not actually validated [17, 18] . They are both com-plex and we consider them to be valid if completed by children without the help of their parents [23] . In this study, all of the children completed the questionnaires on their own.

There is only 1 study evaluating the HRQOL of non-CF BE children in which the DASS (Depression, Anxiety

Table 2. SF-36 and SGRQ subscales had an inverse correlation

SGRQ SF-36 PCS SF-36 MCS

Symptoms score rp

0.4660.001

0.3960.005

Activity score rp

0.6660.000

0.5330.000

Impact score rp

0.6670.000

0.5120.000

Total score rp

0.7050.000

0.5540.000 25.00 R Sq linear = 0.400

20.00 40.00 60.00a SGRQ symptoms score

80.00 100.00

50.00

75.00

100.00

125.00

FEV

1 %

pre

dic

ted

0 R Sq linear = 0. 7

20.00 40.00 60.00SGRQ symptoms score

80.00 100.00

2.00

4.00

6.00

8.00

10.00

Follo

p p

erio

d

year

s

0

R Sq linear = 0.54

20.00 40.00 60.00SGRQ symptoms score

80.00 100.00

2.00

4.00

6.00

8.00

10.00

nti

ioti

c re

qen

cyye

ar

Fig. 1. Correlation of SGRQ symptoms score with FEV 1 , follow-up period and antibiotic frequency. a SGRQ symptoms score corre-lates with FEV 1 (r = 0.417, p = 0.003). b SGRQ symptoms score correlates with regular follow-up (r = 0.3, p = 0.04). c SGRQ symp-toms score correlates inversely with frequent antibiotic require-ments (r = 0.303, p = 0.035).

Dow

nlo

ade

d b

y:

Uni

vers

itt Z

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ch,

Zen

tral

bib

lioth

ek Z

rich

198

.14

3.58

.44

- 6

/14/

201

5 2:

58:3

4 P

M

98

ManagementQuality of life

Significantly lower sleep quality (37 vs 17%; p < 0.05)*

Sleep disordered breathing more frequent (22 vs 9%; p = 0.003)**

Variables associated with lower sleep quality: Sputum Wheezing CT-score Snoring

Erdem E. Pediatr Pulmonol 2011;46:919926

* Pittsburgh Sleep Quality Index (PSQI)** Pediatric Sleep Questionnaire (PSQ) were

99

ManagementLongitudinal growth and lung function

Bastardo CM. Thorax 2009;64:246251

Adequate growth over time

Lung function stabilises but does not normalise with treatment

Need for early detection and institution of appropriate therapy

100

ManagementMicrobiology

0

10

20

30

40

50

60

70

80

7.2 (1.6-19)

12.1 (3-18)

10.0 (1-17)

2.3 (0.7-10)

5.25 (2-16)

7.4 (1-17)

7.3 (1-13)

H.influenzae

S. pneumoniae

M. catarrhalis

P. aeruginosa

S. aureus

Apergillus sp

no pathogens

Studies (mean age (range))

Per

cent

(%)

Grimwood K. Paediatr Respir Rev 2011;12: 111118

101


Kapur N. Pediatr Pulmonol 2012;47:300307

113 children with newly diagnosed non-CF bronchiectasis

102


Kapur N. Pediatr Pulmonol 2012;47:300307

103

Tunney MM. Am J Respir Crit Care Med 2013;187:1118-26


Clinically stable patients Non significantly lower bacterial

counts in patients with chronic maintenance therapy

104


Similar patterns of phyla distribution when clinically stable and at the start of treatment for an exacerbation

No significant difference in microbial community diversity (Shannon-Wiener diversity index)

Abundance of the predominant bacteria decreases slightly after treatment


105






106





Tunney MM. Am J Respir Crit Care Med 2013;187:1118-26 107

As natural history of bronchiectasis and mortality has altered with improvements in health and the environment suggests that with the implementation of other preventative factors, the progression of bronchiectasis could be ameliorated in the majority of children.

Children at risk of bronchiectasis can have normal lungs with early diagnosis and appropriate management

Appropriate treatment reduces exacerbations of bronchiectasis.

Prevention

Chang AB. Pediatr Respir Rev 2011; 12:97-103 108

Early and intensive treatment improves lung function in children with reduced FEV1 at diagnosis and prevents deterioration in the following 2-5 year period

Frequency of exacerbation with hospitalization is significant predictor of FEV1 decline (over 3- yrs)

With each exacerbation, the FEV1%predicted decreased by 1.95% In a Turkish study of 111 children, intensive medical treatment (prompt

antibiotic use, physiotherapy, bronchodilators) reduced exacerbation rates from 6.6 4 to 2.9 2.9 per year

Prevention

Bastardo Thorax 2009;64:24651Kapur Chest 2010;138:15864

Karadag B. Respiration 2005;72:2338. 109

Chronic wet cough is not normal: have a close look at these children Some children may need prolonged antibiotic treatment, whenever

possible according to microbiology Airway damage can be limited by intensive treatment, even in those

predestined to have bronchiectasis Children with high risk to develop bronchiectasis should be carefully

followed up Mucociliary disorders Immune dysfunction Rheumatic inflammatory conditions

Role of vaccinations: Measles, Pertussis, Pneumococcal vaccination

Prevention

Chang CC. Cochrane Database Syst Rev 2009;(Issue):2.110

Prevention

Chang AB. Pediatrics 2013;131:e1576e1583

111

Prevention

Primary prevention Secondary prevention Tertiary prevention

Normal lung development Early detection Reduce morbidity, mortality and secondary complications

Removal of modifiable risk factors

Appropriate treatment Reduce adverse events from medication

ARIs, CSLD, Bronchiectasis

Environmental health (hygiene, sanitation, pollution)

Good follow up of all acute respiratory episodes

Assessment for treatable causes

Identification of predispositions to recurrent ARIs and CSLD

Early diagnosis of bronchiectasis

Prevent exacerbations trough optimization of treatment

Early treatment of exacerbations

Asthma Obtain good asthma control

Chang AB. Pediatr Respir Rev 2014; 15:325-332112

TherapyMainstays

1. Airway clearance techniques

2. Aerosol therapy

3. Antibiotics (inhaled and systemic)

4. Regular exercise

5. Surgery

6. Vaccinations

Annual influenza vaccination

5yearly Pneumococal vaccination

113

TherapyAirway clearance techniques

1. Airway clearance techniques

1. Oscillatory PEP devices: Flutter, Cornett, Acapella

2. Huffing / autogenic drainage selective breathing

2. Chest physiotherapy

3. Trampoline

4. Exercise

5. High- frequency chest wall percussion

114

TherapyAerosol therapy

1. Bronchodilators

No clear evidence

2. Hyperosmolar agents

Hypertonic saline, mannitol

3. Inhaled antibiotics

No evidence

4. Inhaled corticosteroids

No studies

115

TherapyAntibiotics

1. Treatment of exacerbation

According to severity: oral / intravenous

Empiric or guided by microbiology

2. Intermittent therapy

Reduction of bacterial load: inhaled / oral

Guided by microbiology

3. Long-term treatment

Co-amoxicillin in infants?

Azithromycin?

Rubin BK. Semin. Respir. Crit. Care Med. 2003;24:619-27Rubin BK. J Aerosol Med. 2008; 21: 1-6

116

TherapyAntibiotics

Indigenous Australian, Maori, and Pacific Island children aged 18 years

Either bronchiectasis or chronic suppurative lung disease

multicentre, double- blind, randomised, parallel-group, placebo-controlled trial

Eligible children had had at least one pulmonary exacerbation in the previous 12 months

Azithromycin (30 mg/kg) or placebo once a week for up to 24 months

Valerie PC. Lancet Respir Med 2013; 1: 61020

117

TherapyAntibiotics


118

TherapyAntibiotics


119

TherapyAntibiotics


120

TreatmentMacrolides

Rate of bronchiectasis exacerbation

Gao YG. PlosOne; 2014; 9: 3: e90047

121

TreatmentMacrolides

Spirometric indices of FEV1 and FVC

Gao YG. PlosOne; 2014; 9: 3: e90047

122

TherapySurgery

1. Rarely indicated

2. Significant symptoms unable to be controlled by medical therapy

3. Localised disease

One lobe

4. Treatment of complications

empyema, recurrent haemoptysis, lung abscess

Haciibrahimoglu G. Intern. Med. J. 2006; 36: 72937Sirmali M. Eur. J. Cardiothorac. Surg. 2007; 31: 1203

123

Conclusions

1. Bronchiectasis in children is not that rare

2. Often a consequence from chronic infections and suppurative lung disease

3. A detailed look to primary diseases associated with bronchiectasis

4. Management and treatment similar to that in cystic fibrosis

5. Prevention is important and often possible

6. Surgery is rarely indicated

124

Acute Bronchiolitis prevention, diagnosis, and approaches to management

Prof. Fabio Midulla Paediatric Departments. Sapienza University of Rome.

Viale Regina Elena 324 00161 Rome

ITALY [email protected]

AIMS

Clarify definition and aetiology of bronchiolitis Discuss diagnosis and criteria for hospitalization Define the treatment Discuss criteria for discharge

SUMMARY Bronchiolitis is an acute viral respiratory infection involving the terminal and respiratory bronchiole in infants [1]. It is clinically defines as a seasonal viral illness in infants

According to the American academy of Paediatrics oxygen should be administered only when saturation at room air is 95% [9]. Oxygen is usually administered via nasal cannula or a head box. Recent evidence shows that oxygen can be given efficaciously with heated humidified high flow nasal cannula [10-11]. Its presumed role is the reduction of the work of breathing, prevention of dynamic airways collapse and improvement of gas exchange [12]. Current clinical evidence shows that albuterol produce small short-term improvements in clinical scores. A trial with albuterol is justified in infants with severe respiratory distress and it should be continued only if clinical examination documents a significant clinical response [13]. Nebulized racemic adrenalin provides better short-term improvement in the clinical score than placebo, particularly in the first 24 hours. Clinical trials have showed that adrenalin to be superior to placebo and albuterol [14]. A recent Cochrane Review of seven trials showed that nebulized 3% hypertonic saline alone or together with a bronchodilator effectively reduces the length of hospitalization among infants with non severe acute viral bronchiolitis and improve s clinical severity scores in out patients and inpatients populations [15]. On the contrary, two very recent randomized and double blind multicenter studies have showed no clinical effects of nebulized hypertonic saline in children with bronchiolitis. Teunisses et al. have compared the effects of hypertonic saline 3%, and 6% vs 0.9% in infants with moderate-severe bronchiolitis and they have showed non significant difference in the duration of oxygen therapy and tube feeding between the three groups [16]. Everard et al have showed no difference in the time for discharge between infants with bronchiolitis treated with hypertonic saline or placebo [17]. Current evidence provides no support for a clinical beneficial effect of systemic or inhaled glucocorticoids [18]. No evidence justified using antibiotics in bronchiolitis because it is a viral disease and affect infants rarely undergo bacterial superinfection. Antibiotic treatment should be recommended only in infants with severe bronchiolitis requiring intubation, a group in whom bacterial superinfection is more common [19]. Nebulized DNAse and monetelukast are not indicated in the treatment of bronchiolitis [20]. Preventive measures include adequate healthcare professional education about epidemiology and control of viral infection, such as washing the hands before and after caring for patients with viral respiratory symptoms [21]. Palivizumab is a humanized monoclonal RSV antibody. It prevents hospital admission for RSV infections, but do not decrease length of stay or oxygen require for those that are hospitalized. Palivizumab is a useful therapeutic option in infants

REFERENCES 1. American Academy of Pediatrics. Subcommitte on Diagnosis and Management of Bronchiolitis.

Diagnosis and management of bronchiolitis. Pediatrics 2014;134:e1474-e1502 2. Hasegawa K, Tsugawa Y, Brown DF et al. Trends in bronchiolitis hospitalizations in the United

States, 2000-2009. Pediatrics. 2013; 132(1):28-36. 3. Midulla F, Scagnolari C, Bonci E, et al. Respiratory syncytial virus, human Bocavirus and

rhinovirus bronchiolitis in infants. Arch Dis Child 2010 Jan; 95(1):35-41. 4. Ricart S, Marcos MA, Sarda M, et al. Clinical risk factors are more revelant than respiratory

viruses in predicting bronchiolitis severity. Pediatr Pulmonol 2013; 48(5):456-463. 5. Breese Hall C, Weinberg GA, Blumkin AK, et al. Breeze H et al. Respiratory Syncytial Virus

Associated Hospitalizations Among Children Less Than 24 Months of Age. Pediatrics 2013; 132:e341-e348.

6. Corrard F, de La Rocque F, Martin E, et al. Food intake during the previous 24 h as a percentage of usual intake: a marker of hypoxia in infants with bronchiolitis: an observational, prospective, multicenter study. BMC Pediatr 2013; 13:6.

7. Schuh S, Freedman S, Coates A, et al. Effect of oximetry on hospitalization in bronchiolitis: a randomized clinical trial. JAMA. 2014; 312(7):712-8.

8. Oakley E, Borland M, Neutze J, et al. Nasogastric hydration versus intravenous hydration for infants with bronchiolitis: a randomised trial. Lancet Respir Med 2013; 1(2):113-20.

9. Scottish Intercollegiate Guideline Network (SIGN). Bronchiolitis in children. A national guidelinen 91. Edinburg, SIGN, 2006.

10. McKiernan C, Chua LC, Visintainer PF, et al. High flow nasal cannulae therapy in infants with bronchiolitis. J Pediatr 156:634-638.

11. Mayfield S, Bogossian F, O'Malley L, et al. High-flow nasal cannula oxygen therapy for infants with bronchiolitis: pilot study. J Paediatr Child Health 2014; 50(5):373-8.

12. Milsi C, Boubal M, Jacquot A, et al. High-flow nasal cannula: recommendations for daily practice in pediatrics. Ann Intensive Care 2014; 4:29.

13. Gadomski AM, Brower M. Bronchodilators for bronchiolitis. Cochrane Database Syst Rev. 2010; (12):CD001266.

14. Hartling L, Bialy LM, Vandermeer B,et al. Epinephrine for bronchiolitis. Cochrane Database Syst Rev 2011; (6):CD003123.

15. Zhang L, Mendoza-Sassi RA, Wainwright C, et al. Nebulized hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev 2008; (4):CD006458.

16. Teunissen J, Hochs AH, Vaessen-Verberne A, et al. The effect of 3% and 6% hypertonic saline in bronchiolitis. Eur Respi J 2014; 44:913-921.

17. Everard M, Hind D, Ugonna K et al. SABRE: a multicentre randomized control trial of nebulised hypertonic saline in infants hospitalized with acute bronchiolitis. Thorax 2014; 69:1105-1112.

18. Fernandes RM, Bialy LM, Vandermeer B, et al. Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database Syst Rev 2013; 6:CD004878.

19. Spurling GK, Doust J, Del Mar CB, et al. Antibiotics for bronchiolitis in children. Cochrane Database Syst Rev (2011) 6:DC005189.

20. Nenna R, Tromba V, Berardi R, et al. Recombinant human deoxyribonuclease treatment in hospital management of infants with moderate-severe bronchiolitis. Eur J Inflamm 2009; 7:169-174.

21. Sacri AS, De Serres G, Quach C, et al. Trasmission of acute gastroenteritis and respiratory illness from children to parents. Pediatr Infect Dis J 2014;33(6):583-588

22. Andabaka T, Nickerson JW, Rojas-Reyes, et al. Monoclonal antibodiey for reducing the risk of respiratory syncytial virus infection in children. Cochrane Database Syst Rev (2013);4: CD006602

23. Midulla F, Nicolai A, Ferrara M, et al. Recurrent wheezing 36 months after bronchiolitis is associated with rhinovirus infections and blood eosinophilia. Acta Paediatrica 2014; 103:1094-1099.

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http://www.ncbi.nlm.nih.gov/pubmed/?term=Corrard%20F%5BAuthor%5D&cauthor=true&cauthor_uid=23311899http://www.ncbi.nlm.nih.gov/pubmed/?term=de%20La%20Rocque%20F%5BAuthor%5D&cauthor=true&cauthor_uid=23311899http://www.ncbi.nlm.nih.gov/pubmed/?term=Martin%20E%5BAuthor%5D&cauthor=true&cauthor_uid=23311899http://www.ncbi.nlm.nih.gov/pubmed/?term=corrad+Food+intake+during+the+previous+24+hhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Schuh%20S%5BAuthor%5D&cauthor=true&cauthor_uid=25138332http://www.ncbi.nlm.nih.gov/pubmed/?term=Freedman%20S%5BAuthor%5D&cauthor=true&cauthor_uid=25138332http://www.ncbi.nlm.nih.gov/pubmed/?term=Coates%20A%5BAuthor%5D&cauthor=true&cauthor_uid=25138332http://www.ncbi.nlm.nih.gov/pubmed/?term=Schuh+Effect+of+oximetry+on+hospitalization+in+bronchiolitishttp://www.ncbi.nlm.nih.gov/pubmed/?term=Oakley%20E%5BAuthor%5D&cauthor=true&cauthor_uid=24429091http://www.ncbi.nlm.nih.gov/pubmed/?term=Borland%20M%5BAuthor%5D&cauthor=true&cauthor_uid=24429091http://www.ncbi.nlm.nih.gov/pubmed/?term=Neutze%20J%5BAuthor%5D&cauthor=true&cauthor_uid=24429091http://www.ncbi.nlm.nih.gov/pubmed/?term=Oakley+Nasogastric+hydratation+vs+intravenoushttp://www.ncbi.nlm.nih.gov/pubmed/?term=McKiernan%20C%5BAuthor%5D&cauthor=true&cauthor_uid=20036376http://www.ncbi.nlm.nih.gov/pubmed/?term=Chua%20LC%5BAuthor%5D&cauthor=true&cauthor_uid=20036376http://www.ncbi.nlm.nih.gov/pubmed/?term=Visintainer%20PF%5BAuthor%5D&cauthor=true&cauthor_uid=20036376http://www.ncbi.nlm.nih.gov/pubmed/?term=Mayfield%20S%5BAuthor%5D&cauthor=true&cauthor_uid=24612137http://www.ncbi.nlm.nih.gov/pubmed/?term=Bogossian%20F%5BAuthor%5D&cauthor=true&cauthor_uid=24612137http://www.ncbi.nlm.nih.gov/pubmed/?term=O%27Malley%20L%5BAuthor%5D&cauthor=true&cauthor_uid=24612137http://www.ncbi.nlm.nih.gov/pubmed/?term=Mayfield+HFNC+oxygen+therapy+for+infants+with+viralhttp://www.ncbi.nlm.nih.gov/pubmed/25593745http://www.ncbi.nlm.nih.gov/pubmed/25593745http://www.ncbi.nlm.nih.gov/pubmed/?term=Gadomski%20AM%5BAuthor%5D&cauthor=true&cauthor_uid=21154348http://www.ncbi.nlm.nih.gov/pubmed/?term=Brower%20M%5BAuthor%5D&cauthor=true&cauthor_uid=21154348http://www.ncbi.nlm.nih.gov/pubmed/21154348http://www.ncbi.nlm.nih.gov/pubmed/21154348http://www.ncbi.nlm.nih.gov/pubmed/21678340http://www.ncbi.nlm.nih.gov/pubmed/?term=Zhang%20L%5BAuthor%5D&cauthor=true&cauthor_uid=18843717http://www.ncbi.nlm.nih.gov/pubmed/?term=Mendoza-Sassi%20RA%5BAuthor%5D&cauthor=true&cauthor_uid=18843717http://www.ncbi.nlm.nih.gov/pubmed/?term=Wainwright%20C%5BAuthor%5D&cauthor=true&cauthor_uid=18843717http://www.ncbi.nlm.nih.gov/pubmed/?term=Zhang+L+Nebulized+hypertonic+saline+solution+for+acute+bronchiolitis+in+infantshttp://www.ncbi.nlm.nih.gov/pubmed/?term=Teunissen%20J%5BAuthor%5D&cauthor=true&cauthor_uid=24969648http://www.ncbi.nlm.nih.gov/pubmed/?term=Hochs%20AH%5BAuthor%5D&cauthor=true&cauthor_uid=24969648http://www.ncbi.nlm.nih.gov/pubmed/?term=Vaessen-Verberne%20A%5BAuthor%5D&cauthor=true&cauthor_uid=24969648http://www.ncbi.nlm.nih.gov/pubmed/23733383http://www.ncbi.nlm.nih.gov/pubmed/23733383http://www.ncbi.nlm.nih.gov/pubmed/24948158http://www.ncbi.nlm.nih.gov/pubmed/24948158

EVALUATION 1. A 50 days old infant was admitted to the paediatric Emergency Room for loss of appetite and

increased work of breathing, started 4 hours before. Parents reported that the child had rhinitis and cough in the last 5 days, with mild fever that last 2 days (T max 37.7 C). On physical examination, the infant appears alert and responsive with a moderate degree of dehydration. He had intercostal and jugular retractions. The heart rate was 120 bpm, respiratory rate was 58 per minute and SpO2 was 95% at room air. Lung auscultation shows diffuse fine a rapid test in the nasal wash sample was positive for Respiratory Syncytial Virus.

What could be the diagnosis of this child?

a. Whooping cough b. Pneumonia c. Flu d. Bronchiolitis e. Wheezing bronchitis

2. A one month old girl was admitted to the paediatric Emergency Room for cough followed by vomiting. The mother reports that as a result of coughing the child seems to remain "out of breath" and has also perioral cyanosis. On physical examination, the child looks slightly exhausted but responsive. There was no evidence of respiratory distress. The heart rate was 126 bpm, respiratory rate 62 per minute and SpO2 to 98% at room air, but decreased to 89% during paroxysmal cough. Lung auscultation was negative, as well as cardiac and abdominal examination. Blood tests showed the following picture: WBC 15630/mm3 (N 38.2%, 63.6% L, and E 0.7%), C reactive protein 0.54 mg/dl, Hb 13.5 g/dl.

What could be the diagnosis?

a. Pneumonia b. Bronchiolitis c. Whooping cough d. Flu e. Wheezing bronchitis

3. A 40 days old infant is admitted to the paediatric emergency room for a mild respiratory distress

(RR = 65 per minute and intercostal retractions), preceded few days before by rhinitis, cough and low grade fever. Lung auscultation reveals bilateral fine rales. SpO2 at room air was 95%.

What kind of therapy you plan to start?

a. No medical therapy, only clinical observation b. Aerosol therapy with salbutamol c. Aerosol therapy with adrenaline and 3% hypertonic solution d. Antibiotic therapy e. HHFNC

128

Acute Bronchiolitis prevention, diagnosis, and approaches to management

Fabio Midulla MD

Paediatric Department

129

Conflict of interest disclosure

I have no, real or perceived, direct or indirect conflicts of

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