Respiratory hour - 3

Continue Asthma Extrathoracic 1) Neonatal respiratory distress

syndrome and its complications 2) Cystic Fibrosis 3) Sickle cell patients: acute chest

syndrome 4) SIDS

Pediatric AsthmaEpidemiology, Pathophysiology, and Initial Evaluation

Overview

Chronic disease of the lower airways, characterized by reversible airway obstruction, inflammation, and bronchial hyper-responsiveness

Leads to recurrent episodes of wheezing, breathlessness, chest tightness and coughing

Epidemiology

Most frequently encountered pulmonary disease in children

The lifetime prevalence of asthma in children is 13%

Prevalence rates are highest among Puerto Rican and African American children

Among the most common reasons for hospitalizations in the pediatric practice (3% of all pediatric admissions in 2004)

Epidemiology

Mortality

Although mortality rates have fallen, asthma remains a preventable cause of death in children

In 2004, the mortality rate from asthma was 2.5 per 1 million children (186 deaths)

In general, the rate of death of asthma is higher in severe, uncontrolled disease

Mortality

Risk factors for mortality due to asthma include:

One or more life threatening exacerbations of asthma

Severe asthma requiring chronic oral corticosteroids

Poor control of daily asthma symptoms Abnormal Forced Expiratory Volume in one

second (FEV1) Frequent ED visits Low socioeconomic status Family dysfunction Patient psychological problems

Risk Factors

Factors Influencing the Development and Expression of Asthma

GeneticGenes predisposing to atopyGenes predisposing to airway hyper

responsivenessObesitySex

Boys affected more often than girls prior to adolescence

Risk Factors Environmental Risk Factors

Allergens Indoor – Domestic mites, furred

animals (dogs, cats, mice),cockroach allergens, fungi, molds, yeasts.

Outdoor – Pollens, fungi, molds, yeasts.

Infections (predominantly viral)Occupational sensitizersTobacco Indoor/Outdoor air pollutionDiet

Pathophysiology Inherent to asthma is

airway inflammation, which is mediated by a variety of cell subtypes

Airway inflammation results in hyper-responsive airways, which limits airflow and causes the variable clinical symptoms

Acute phase Late-phase

Release of inflammatory mediators

IgE

Mast cell

Allergen

Muscle contraction

Mucus secretion

Recruitment of leukocytes

Epithelial cell injury

Muscle contraction

Mucus secretion

Atopic asthma

Pathophysiology

Pathophysiology

Inhaled allergens are ingested by Antigen Presenting Cells (APCs) which then present pieces of the allergen to other immune system cells (TH0 cells)

In asthmatic patients, these TH0 cells transform into TH2 cells, which activates the humoral immune system, creating antibodies against the inhaled allergen

All subsequent times the allergen is inhaled, these antibodies recognize it and activate the humoral response

Proinflammatory cytokines (IL-4, IL-5, IL-13) produced primarily by TH2 cells are believed to trigger the intense inflammation of allergic asthma

The imbalance between TH1 and TH2 lymphocytes contributes to chronic inflammatory asthma

Pathophysiology

IgE mediated “early phase” is the immediate response to an allergen, which causes mast cells and basophils to degranulate, precipitating bronchospasm as well as the release of proinflammatory cytokines and chemokines

This cascade of inflammatory response results in the subsequent “late phase” obstruction of air flow, which occurs 4-12 hours following exposure to the environmental insult

Pathophysiology

Pathophysiology

Asthma can also be characterized at the cellular level by structural alterations in the airway epithelium

Airway remodeling components: Mucus gland hyperplasia Thickening of the epithelial basement membrane Fibrotic changes in the sub-basement membrane Bronchial smooth muscle hypertrophy Angiogenesis

Pathophysiology

Clinical Aspects

Tools for Diagnosis of Asthma in the Pediatric Population

Good History Taking (ASK)

Careful Physical Examination (LOOK)

Investigations (PERFORM)

Clinical Aspects

Detailed Medical History (HPI, PMH, FMH)

Does the child cough, wheeze, or develop chest tightness after exposure to airborne allergens or irritants e.g. smoke, perfumes, animal fur?

Does the child’s cold frequently ‘go to the chest’ or take more than 10 days to resolve?

Does the child use any medication when symptoms occur? How often?

Are symptoms relieved when medication is used?

Clinical Aspects

Physical Examination

General attitude and well being Deformity of the chest Character of breathing Thorough auscultation of breath sounds Signs of any other allergic disorders on the

body Growth and development status

Clinical Aspects

Signs and Symptoms of Asthma Recurrent Wheeze Recurrent Cough Recurrent Breathlessness Activity Induced Cough/Wheeze Nocturnal Cough/Breathlessness Tightness Of Chest Afebrile episodes Personal atopy Family history of atopy or asthma History of triggers Seasonal exacerbations Relief with bronchodilator

Clinical Aspects

Clinical InvestigationsSpirometry

2007 Guidelines recommend objective measurement of pulmonary function as part of the initial evaluation

Spirometry is a pulmonary function test that measures the volume of air an individual inhales or exhales as a function of time

Should be performed before and after administration of a short-acting bronchodilator (≥12% increase in FEV1 suggests asthma)

LIMITATIONS: Can’t be performed on children less than 6 years old

Clinical Aspects

Baseline chest radiographs Typically show mild hyperinflation and/or

increased bronchial markings

Peak flow monitoring- may be useful for patients with moderate to severe asthma

50-80% of predicted = mild to moderate <30% of predicted = severe obstruction LIMITATIONS: heavily dependent on

technique

Differential Diagnosis

A child presents with wheezing and respiratory distress:

Intraluminal inflammation or failure to clear secretions (bronchiolitis, gastroesophageal reflux with aspiration, cystic fibrosis, tracheoesophageal fistula, primary ciliary dyskinesia)

Intraluminal mass effects (foreign body aspiration, tracheal/bronchial tumors, granulation tissue)

Dynamic airway collapse (tracheobronchomalacia) Intrinsic narrowing of the airway (congenital or

acquired stenosis) Extrinsic compression (vascular ring, mediastinal

lymph nodes or masses)

Differential Diagnosis

The Early Wheezer (<3 years old)

Broncholitis in children Most common cause of wheezing in children aged 6 months to 3 years

old Diagnosis is mainly clinical Commonly due to Respiratory Syncytial Virus (RSV) Symptoms: Rhinorrhea, Pharyngitis, Cough, Low grade fever,

Wheezing, Tachypnea

Wheeze associated lower respiratory

tract infection

Early Onset Asthma

• Febrile episodes• Personal atopy absent• Family history of

asthma/atopy absent• Variable response to

bronchodilators

• Afebrile episodes• Personal atopy

present• Family history of

asthma/atopy present• Perdictable good

response to bronchodilators

Differential Diagnosis

Age Common Uncommon Rare

<6 months

BroncholitisGastroesophageal Reflux

Aspiration PneumoniaBronchopulmonary DysplasiaCongestive Heart FailureCystic Fibrosis

AsthmaForeign Body Aspiration

6 months - 2 years

BroncholitisForeign Body Aspiration

Aspiration PneumoniaAsthmaBronchopulmonary DysplasiaCystic FibrosisGastroesophageal Reflux

Congestive Heart Failure

2-5 years AsthmaForeign Body Aspiration

Cystic FibrosisGastroesophageal RefluxViral Pneumonia

Aspiration PneumoniaBroncholitisCongestive Heart Failure

Jog your memory slide

What sign to you see? Omega sign made by the epiglottis collapse of? supraglottic structures? the arytenoid cartilages and epiglottitis When? inspiratory stridor Laryngomalacia

What is malacied here? Trachea Tracheomalacia The hallmark? expiratory wheeze, hx of trauma due to? Mechanical ventilation

Asthma is a disease of airway inflammation “early phase” is the immediate response to an allergen, which

causes __?___to degranulate? mast cells and basophils, which in turn precipitates? bronchospasm as well as the release of proinflammatory

cytokines and chemokines One of the most important risk factor for the development of

asthma is ? Atopy

Practical Management of Asthma

Initial Assessment Once asthma has been diagnosed, the

degree of severity needs to be determined Severity is best determined at the time of

diagnosis, before the initiation of therapy Severity can be divided into four categories

1. Intermittent2. Mild Persistent3. Moderate Persistent4. Severe Persistent

*All individuals who have persistent asthma require long-term control medication

Initial Assessment (continued) Identify and address precipitating factors (asthma

“triggers”) Prick skin testing or blood testing (IgE) to detect

sensitization to common indoor allergens The most effective programs to reduce indoor

allergens are intensive, multifaceted interventions that address more than one allergen Common allergens

House dust mite reduce indoor humidity, laundering bedding in hot water, reducing “dust catchers”

Cockroach antigen pest management program Screen for comorbid conditions

Infection, obesity, depression in child or parent, gastroesophageal reflux, allergies, obstructive sleep apnea

Medical Management Two types of medication are used to

treat asthma 1. Long-term control (“prevention”)

medications Inhaled corticosteroids (ICSs) are the medication of

choice for all individuals suffering persistent asthma

2. Quick relief medications Reverse acute airflow obstruction

Children 0 to 4 Years

Children 0 to 4 Years

Children 0 to 4 Years

Children 5 to 11 Years

Children 5 to 11 Years

Children 5 to 11 Years

Youth 12 years of age and Older

Youth 12 years of age and Older

Youth 12 years of age and Older

Corticosteroids Inhaled corticosteroids are first line therapy for chronic

asthma Examples

Mometasone Fluticasone Budesonide Beclomethasone Triamcinolone Flunisolide

Mechanism: inhibits the synthesis of virtually all cytokines and inactivates NF-κB (NF-κB is the transcription factor that induces the production of TNF-α and other inflammatory agents)

Toxicity Oral Candidiasis, Dysphonia (hoarseness), Bronchospasm, Reflex

Cough use spacers (VHC) or post-inhalation mouth rinse to prevent

β2-agonists Drugs

Short acting -- used for breakthrough symptoms and during acute exacerbation Albuterol (known internationally as salbutamol) Levalbuterol Others used much less commonly

Terbutaline Metaproterenol (β2, minor β1) Isoproterenol (nonselective)

tachycardia may lead to cardiac death

Long acting -- used for maintenance in combination with inhaled corticosteroid (never without)

Salmeterol Tremors, arrhythmia

Formoterol

Mechanism: β2 receptors are activated on bronchial smooth muscle to achieve bronchodilation. Stimulation of adenylate cyclase leading to closing of calcium channels and ultimately the relaxation of smooth muscles

Methylxanthines Theophylline (rarely used) Mechanism: inhibition of phosphodiesterase,

leading to decreased cAMP hydrolysis which causes bronchodilation metabolized by P-450 blocks actions of adenosine

Toxicity seizures narrow therapeutic index nausea/vomiting arrhythmia

Muscarinic antagonists Drugs

Ipratropium Tiotropium

Mechanism: competitive inhibition of muscarinic receptors prevents bronchoconstriction

Also used for COPD

Cromolyn Prophylaxis only! Ineffective during an acute asthma

attack Mechanism: prevents release of

mediators from mast cells Rare Toxicity

Antileukotrienes Drugs

Zileuton 5-lipoxygenase pathway inhibitor blocks

conversion of arachidonic acid to leukotrienes

Zafirlukast, Montelukast Blocks leukotriene receptors Particularly effective in aspirin-induced

asthma

Omalizumab Clinical use

Severe uncontrolled asthma with elevated IgE Symptoms and activity refractory to standard

therapies and oral glucocorticoids Mechanism: anti-IgE antibody (inhibits

action of IgE with inflammatory cells) Asthma can be caused by uncontrollably high

IgE response Severe allergic reactions may occur

following infusion of omalizumab

Acute Exacerbation Signs and symptoms of a severe exacerbation

Dyspnea at rest Peak flow rate less than 40% of predicted or personal best Accessory muscle use Failure to respond to initial treatment

Initial management includes: Brief assessment Administration of a SABA to reverse airway obstruction

Add inhaled anticholinergic medications for moderate-to-severe exacerbations

Oxygen should be administered to most patients, particularly those experiencing hypoxemia or moderate or severe exacerbation

Systemic corticosteroids should be administered early in the treatment of moderate or severe exacerbations and to any patient who does not respond promptly to initial treatment

QuestionBased on the NHLBI EPR 3 asthma guidelines, the most preferred first step in therapy for moderate persistent asthma would be which of the following?

A. Short-acting beta agonists

B. Low-dose inhaled corticosteroids

C. Low-dose inhaled corticosteroids and long-acting bronchodilator

D. High-dose inhaled corticosteroids and long-acting bronchodilator

0% 0%0%0%

The preferred treatment for moderate persistent asthma is low-dose inhaled corticosteroids and long-acting beta agonists, leukotriene receptor antagonist, or theophylline. Alternative therapy would be medium-dose inhaled corticosteroids.

Question: 12 year old female with a history of moderate persistent asthma presents for routine follow-up. At the time of her initial visit, you prescribed low-dose inhaled steroids and a leukotriene modifier. She reports that since her initial visit, she has had minimal daytime symptoms. She has required her rescue inhaler only 2-3 times a week and awakes form sleep only about 3-4 times a month. She reports that, overall, she feels the medications are working great. She denies significant exercise limitation. She has had no exacerbations requiring oral steroids or acute intervention by another physician. Based on the history provided by the patient, you would classify her control as which of the following?

A. Well controlled B. Not well controlled C. Very poorly controlledD. Unable to assess based on

this information

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The patient meets 2 of the criteria for not well controlled:

1) Symptoms >2 times a week requiring rescue inhaler

2) Nocturnal symptoms >2 times a month The patient also meets 1 criteria for well

controlled: 1) Has had no oral steroids, ER visits, etc.

Therefore, the patient is classified as not well controlled because it is the the most severe category in which her symptoms are consistent

QuestionAll of the following are true regarding mechanisms of action of inhaled glucocorticoid therapy except:

A. Inhibition of cytokine production

B. Inhibition of inflammatory cell recruitment

C. Inhibition of mediator release

D. Decreases microvascular leak therefore decreases edema formation

E. Down-regulation of beta-adrenergic receptors

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Inhaled glucocorticoids actually cause up-regulation of beta-adrenergic receptors. At one time, their use was limited to patients with moderate-to-severe asthma, but now they are recommended as first-line agents for those with mild persistent asthma. Clinically significant adverse reactions are unlikely with appropriate pediatric doses.

Jog your memory slide

Any child with feeding abnormalities, should undergo?

Barium Swallow test What do you see here? Vascular rings Structural Abnormalities of the aortic arch compressi ng trachea and esophagus Stridor, Dysphagia

Nurse unable to pass a? Nasogastric tube (NG) Clinically? Inspiratory stridor cyanosis w/ feeding & resting relieved by crying Choanal atresia/Stenosis nasal passage (choana) 

Asthma is a disease of airway inflammation “early phase” is the immediate response to an allergen, which causes __?___to

degranulate? mast cells and basophils, which in turn precipitates? bronchospasm as well as the release of proinflammatory cytokines and chemokines One of the most important risk factor for the development of asthma is ? Atopy Rule of 2, converts asthma from intermittent to ? Persistant How do you treat differently?

Cystic Fibrosis

Pathophysiology Inherited multisystem disorder in Caucasians,

disordered exocrine gland function

CFTR gene is a cAMP activated chloride channel on apical surface of epithelial cells in airways, pancreatic ducts, biliary tree, intestines, vas deferens and sweat glands.

Chloride anions stay inside the cell-- Dehydration, viscid secretions and impairment of mucociliary clearance.

Pathophysiology: Mutated CFTR gene

Genetics/Epidemiology

Autosomal Recessive- mutations of both alleles of 250,000 bp gene on chromosome 7 called cystic fibrosis transmembrane conductance regulator (CFTR).

Most common defect Delta 508, deletion of 3 bps leading to absence of phenylalanine at codon 508.

1/3500 newborns Class I, II, III most severe defect in CFTR-

severe progressive pulmonary disease and pancreatic insufficiency

Class IV, V- Milder

Clinical ManifestationsRESPIRATORY GASTROINTESTINAL OTHER SYSTEMIC

Chronic productive cough

Protein/fat Malabsorption

Diabetes Mellitus

Lower airways bacterial colonization

Malnutrition/ FTT Digital clubbing

Endobronchial infection

Meconium Ileus Hyponatremic Dehydration

Exercise Intolerance Distal Intestinal obstruction syndrome

Hypochloremic Alkalosis

Hypoxemia Obstructive Jaundice Vitamin A, D, E, K deficiences

Bronchiectesis Focal Biliary Cirrhosis Zinc deficiency Dermatitis

Pneumothorax Rectal Prolapse Male infertility

Hemoptysis Recurrent Pancreatitis Nasal polyposis

Diagnosis Test any child with persistent cough, pneumonia, sinusitis or

unexplained poor weight gain/FTT. Other diagnostic criteria include nasal polyps, rectal prolapse,

hypochloremic alkalosis, or known family history of the disease. Diagnostic tests for CF include: 1-Newborn screening + when increased immunoreactive

trypsinogen (IRT)(pancreatic enzyme) 2-Confirmatory Sweat Chloride Test=Gold standard

Pilocarpine iontoelectrophoresis >60 meq/L -- + 3-DNA analysis (Definitive diagnosis with 2 CFTR mutations)

4-Nasal potential difference test

(After chemical washing, patients with CF show no change in measured electrical potential)

Diagnostic Criteria BOTH of the following criteria must be met to

diagnose CF 1- Clinical symptoms of CF in at least one

organ system AND 2- Evidence of CFTR dysfunction ( any of the

following) Elevated sweat chloride >60 mmol/L on two

occasions Presence of 2 disease causing mutations in

CFTR from each parental allele Abnormal nasal potential difference.

LUNG DISEASE Progressive, obstructive lung disease with

thickening of airway mucus. Destroys lung parenchyma, predominantly in conducting and respiratory airways. Can lead to fibrotic cavitations and diffuse cystic changes seen on CXR.

LUNG DISEASE

On PE: Coarse crackles, absent air movement, tachypnea, air trapping and increased A/P chest diameter.

Other findings include: Hypoxemia, exercise intolerance, wt loss and decreased pulmonary function

Can assess FEV1, FEF 25-75 and lung volume measurements

6-10 years pathogenic organism Staph Aureus 25-34 years Pseudomonas Aerginosa Advanced CF: Burkholderia cepacia associated with

poor overall outcome

Complications Pulmonary hemorrhage and spontaneous

pneumothorax. Due to airway inflammation that erodes the

bronchial artery. Massive hemoptysis of >500 ml in 24 hours will

require acute arterial embolization.

Pulmonary therapies Check sputum/bronchoalveolar lavage for

organisms present Keep in mind CF patients clear aminoglycosides

more rapidly and require increase in dosing. Chronic P. aerginosa with inhaled tobramycin daily

every other month 3 times weekly azithromycin Airway Clearance Therapy: percussive and

postural drainage Older patients: oscillating chest vests Hypertonic saline/recombinant human

deoxyribonuclease nebulized Patients with respiratory failure are candidates for

lung transplantation

Postural Drainage

Upper Airway Disease Opacification of maxillofacial sinuses on

radiography Acute sinusitis, sinus tenderness, pressure

headaches, facial swelling Antibiotic therapy for greater than 2 weeks,

depending on organism

NASAL POLYPS: Routine application of nasal steroids, surgical intervention for nasal polyposis

Indication for sweat chloride testing in otherwise healthy child.

Prognosis Median predicted survival in 1985 was 25 years of age, by

2006 has risen to 37 years. If diagnosed early by NBS can live into adulthood. Early diagnosis, aggressive airway clearance therapies,

antibiotics and assessment of comorbidities is important. Respiratory therapy for 60 minutes; 2-3 therapies per day! Local CF centers have resources to help families with

financial need. PCP’s are the first ones to recognize early exacerbations,

give annual influenza vaccine.

Board Review: Clinical Vignette

A 2 year old male comes to your primary care office with the complaint of chronic cough, which has been present since the first few months of life. When he is very physically active he sometimes wheezes. He has an uncle with asthma and his parents have treated his wheezing with the uncles bronchodilator inhaler without discernable improvement. He has two older siblings who are healthy. His height is at the 30th percentile and his weight is below the 5th percentile for his age. His chest is slightly hyperinflated. Auscultation of the chest is normal. While in the examination room he fills his diaper with stool and the odor is foul smelling. On CXR: mild hyperinflation is seen and bronchial thickening but is otherwise unremarkable.

QuestionThe sweat test result is 50 mEq/L and the laboratory reports that the diagnostic value is >60mEq/l. Which of the following in the most appropriate next response?

A. measure pancreatic enzyme concentration in a duodenal aspirate

B. send blood for CFTR genotypingC. reassure the family that the

sweat test is negative and the child does not have CF

D. repeat the sweat chloride testE. send the child to a research

center for the measurement of nasal mucosal electrical potential difference. measu

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Answer D. Repeat the sweat chloride test: If the result

was 50 must repeat. Many patients with CF may have a false negative sweat chloride test.

CTFR genotyping is more expensive and time consuming, but can be used as a primary diagnostic tool.

Respiratory Failure

Respiratory Failure Acute respiratory failure is impairment in

oxygenation or ventilation where PO2 < 60mmHg (acute hypoxemia) PCO2 > 50 mmHg (acute hypercapnia) pH < 7.35.

Respiratory Failure is basically an inability of the respiratory system to meet the metabolic needs of the tissues.

Incidence Respiratory failure is inversely related to age in Peds 2/3rd of cases occur in 1st postnatal year while ½ seen in the neonatal period Several developmental phenomenon are responsible

for the above stats Airway is small with narrowest point in the subglottic

area. The cone shaped larynx is prone to obstruction Thoracic cage is soft, with ribs positioned horizontally

which is a mechanical disadvantage for the chest expansion

The diaphragm fatigues easily due to limited energy stores in infants.

Immature nervous system often triggers bradypnea/apnea

Causes

Failure of oxygenation (Hypoxia) Due to Imbalance of ventilation and

perfusion (V/Q Mismatching)

OR

Due to impairment of oxygen diffusion at the level of alveolar-capillary membrane

Failure of Ventilation (Hypercapnia) Decreased tidal volume (shallow breathing) Decreased Respiratory Rate (bradypnea)

Anoxic Can be improved with increased inspired

oxygen But if it’s a result of shunt, increasing inspired

oxygen doesn’t improve hypoxia Anemic

Oxygen carrying capacity is impaired (Low hemoglobin)

Or Insufficient functional hemoglobin (Hemoglobinopathies)

Stagnant When total blood flow is decreased (Heart

Failure) Maldistribution of blood (Septic shock)

Cytochemical Exogenous or endogenous factors which leads

to malfunctioned diffusion of oxygen at the level of tissue (Cyanide)

Classification of Hypoxia

Causes of Respiratory Failure

Respiratory FailurePediatrics in Review 2009;30;470Mara E. Nitu and Howard Eigen

Respiratory FailurePediatrics in Review 2009;30;470Mara E. Nitu and Howard Eigen

Clinical features: flushing, agitation and tachycardia point to Acute hypercapnia

In this case, lower airway obstruction led to poor ventilation and respiratory failure.

RSV can cause respiratory failure by two mechanisms

1) Lower airway involvement (bronchiolitis as in this case)

2) RSV caused central Apnea. (This is more frequent in young infants than in older children)

Clinical ManisfestationsCase 1

A 4-month-old, previously healthy baby is seen in December for fever, a 4-day history of nasal congestion, and progressive difficulty breathing. Vital signs are: heart rate of 169 beats/min, respiratory rate of 56 beats/min, blood pressure of 126/56mmHg, and oxygen saturation on room air of 92%. The infant is crying but can be consoled. Physical examination reveals intercostal and subcostal retractions, tachypnea, bilateral wheezing, and coarse breath sounds. Capillary refill is brisk and the extremities are warm. A chest radiograph shows peribronchial cuffing and slight hyperinflation suggestive of viral pneumonitis. A swab for respiratory syncytial virus (RSV) is reported as positive. Supplemental oxygen is initiated, viral bronchiolitis is diagnosed, and the infant is admitted for monitoring. A few hours later, he becomes very agitated flushed, and inconsolable. His heart rate is 189 beats/min, respiratory rate is 86 beats/min, and oxygen saturation is 92% on 3 L of oxygen administered by nasal canula. His work of breathing is significantly increased, as demonstrated by nasal flaring, grunting, head bobbing, and significant retractions. The infant is transferred to the intensive care unit for intubation and mechanical ventilation. Arterial blood gas before intubation shows a pH of 7.16 and PCO2 of 70 mm Hg. He is intubated and mechanically ventilated for 4 days.

Case 2

A 9-year-old child who has a history of Down syndrome, mitochondrial myopathy, and tracheostomy is admitted because of a 3-week history of decreased activity and increased somnolence. His respiratory rate is 35 beats/min with very shallow effort. Arterial blood gas reveals: pH, 7.33; PCO2, 62 mm Hg; PO2, 54 mm Hg; and HCO3, 28 mEq/L on room air (0.21 FiO2). Complete blood count reveals polycythemia with a hemoglobin of 15 g/dL (150 g/L) and hematocrit of 48% (0.48). The patient receives 100% oxygen, and subsequent arterial blood gas determination documents pH, 7.23; PCO2, 80 mm Hg; PO2, 118 mm Hg; and HCO3, 32 mEq/L. Chest radiograph reveals mild cardiomegaly and increased pulmonary markings suggestive of chronic lung disease (Fig. 2). Echocardiography shows mild pulmonary hypertension and right ventricular hypertrophy. The patient is placed on home mechanical ventilation to treat chronic respiratory failure.

What’s going on?! Patients with underlying myopathy lack the ability to

increase the work of breathing (first sign of respiratory failure)

Thus, such patients present with tachypnea and very shallow breathing without any rib retractions

The first gas pattern: Typical of Chronic respiratory failure. Mild Respiratory acidosis (increased PCO2) with metabolic compensation (increased bicarb)

Patients with chronic respiratory failure, if given 100% oxygen, can lead to higher retention of carbon dioxide [These patients’ respiratory center is primarily stimulated by hypoxic drive and with 100% oxygenation, this drive gets blunted]

Polycythemia, Pulmonary hypertension and cor pulmonale seen in this patient represents rare complications of chronic hypoxemia.

Chest Radiograph showing Cardiomegaly and increased pulmonary markings [Case 2]

Respiratory FailurePediatrics in Review 2009;30;470Mara E. Nitu and Howard Eigen

History and Physical Examination

Initial Assessment: Urgent medical Intervention Helpful indicators: Vital signs, work of breathing

and level of consciousness

Patient with rapid respirations, significant retractions, head bobbing, nasal flaring, grunting

As patient becomes fatigued, there are more shallow respirations, leading to lack of responsiveness and hypoxemia despite a high FiO2

Aggressive and urgent respiratory support

Emergent airway control and ventilatory support.

Patient presenting with severe hemodynamic compromise, mottled extremeties, and very low blood pressure

Emergent airway control, breathing and circulatory support

If emergent Intervention is not necessary, a comprehensive history can be obtained to determine the probable causes of respiratory failure: Previous fever and ill contacts Possible foreign body aspiration Previous chronic lung disease (Cystic Fibrosis,

Asthma, Prematurity) Causes of central ventilation (drug ingestion, head

trauma and seizures) Physical Signs:

Vital signs (Respiration rate, Heart rate, Blood Pressure) Pulse Oximetry

But it is unreliable for patients with decreased tissue perfusion (shock, hypovolemia or hypothermia)

Clinical Findings: Increased work of breathing Nasal Flaring, substernal retractions, head bobbing, respiratory pauses, grunting and thoracoabdominal asynchrony, shape of the thoracic cage and spine should be noted Asymmetric chest movements, tracheal deviation point at

plueral effusion or pneumothorax

Auscultation: Presence of wheezing or crackles, stridor, decreased breath sounds, heart sounds, palpation of brachial/femoral pulses Asymmetric wheezing Foreign body Aspiration or

mass obstructing the airway Crackles Alveolar process such as Pneumonia Abnormal heart sounds Congenital or acquired heart

disease Palpation of brachial/femoral pulses Help rule out

aortic coarctation

Clinical Findings

Respiratory FailurePediatrics in Review 2009;30;470Mara E. Nitu and Howard Eigen

Intercostal and Substernal retractions

Respiratory FailurePediatrics in Review 2009;30;470Mara E. Nitu and Howard Eigen

Head Bobbing

Respiratory FailurePediatrics in Review 2009;30;470Mara E. Nitu and Howard Eigen

Thoracoabdominal asynchrony

Assessment of Muscle Strength and Gait may point to underlying reason of respiratory failure Decreased muscle strength Duchene muscular

dystrophy or some mitochondrial diseases Delayed or loss of motor milestones first clues

to severe myopathy Lack of attaining head control Spinal muscular

atrophy Acute ascending paralysis . Guillain-Barre

Syndrome Acute generalized muscle weakness Botulism

Assessment of mental status using Glasgow Coma Scale (GCS) Decreased GCS Impaired Neurologic function GCS < 8 Airway control by intubation and

mechanical ventilation

Laboratory and Radiographic EvaluationArterial blood gas Assesses the extent of hypoxemia or hypercapnia

• Blood gas analysis should be correlated with the clinical picture• A normal PCO2 with high work of breathing and severe

tachypnea reflects respiratory failure• Normal PCO2 with severe metabolic acidosis and tachypnea

impending respiratory failure

Respiratory FailurePediatrics in Review 2009;30;470Mara E. Nitu and Howard Eigen

Complete blood count Anemia can be associated with chronic

illness and polycythemia and obstructive sleep apnea

Chest Radiograph Pneumonia, Pulmonary edema, Pneumothorax,

or pleural effusion

Pulmonary function testing Characterize the respiratory disease, it’s

severity, course of illness and response to therapy

Management Close monitoring and supplemental oxygen to full

mechanical ventilatory support. Rapid initial assessment Emergency intervention,

preparation for intubation and mechanical ventilation Bag-mask ventilation with 100% oxygen (For proper

ventilation) Intubation

Neuromuscular blockade can be used as well for difficult airway management.

Laryngeal mask airway (LMA) is another option if intubation is difficult (LMA has it’s limitation since it doesn’t protect against aspiration in the patient who hasn’t been fasting)

If no emergency intervention needed: Mild cases Supplemental oxygen delivered via

nasal canula If O2 requirements high nonrebreather mask can be

used, that delivers high flow O2 at 10-15L/min NonInvasive Mechanical Ventilation

CPAP or BiPAP [The risk of developing sores on the face limits prolonged use

of noninvasive mechanical ventilation for 24 hours a day] BiPAP can be used at home for chronic respiratory failure to

postpone the need for tracheostomy or home mechanical ventilation or who choose not to use other interventions.

Conventional treatment of acute respiratory failure Positive pressure ventilation + Supplemental O2 Ventilation with elevated O2 concentrations and

airway pressure has been shown to worsen lung injury [Ventilator induced lung injury (VILI)]. Thus goal is to minimize lung injury while

providing effective ventilation and oxygenation

An FiO2 > 0.6 used for longer than 6 hours is believed o add oxidative stress to the ventilated lungs and contribute to VILI

At present, use of lowest possible pressures and volumes to maintain acceptable ventilation and oxygenation is recommended.

The instillation of surfactant and inhaled nitric oxide (iNO) can supplement mechanical ventilation in carefully select patients. Intratracheal instillation of surfactant in preterm infants has

significantly improved the outcome of RDS

iNOS is an adjunctive therapy for patients who have documented or suspected pulmonary hypertension and significant oxygenation failure.

If adequate gas exchange can’t be achieved with conventional mechanical ventilation High frequency ventilation is a good therapeutic option.

When all options have failed to provide adequate gas exchange and hemodynamic support Extracorporeal membrane oxygenation (ECMO)

Weaning from mechanical ventilation is achieved gradually as the underlying pathologic process resolves.

Summary There are many conditions that can lead to

respiratory system to meet the metabolic needs of the tissues

Prompt interventions and close monitoring in the critical care setting is important to avoid cardiorespiratory arrest secondary to unrecognized respiratory failure.

Clinical interventions range from non invansive methods to intubation and mechanical ventilation to ECMO as the last resort

Jog your memory slide

•If you get a child with respiratory distress and ABG reveals an oxygen tension of 45 mm Hg and a carbon dioxide tension of 60 mm Hg. What should you do?•Intubate- insert Endotracheal tube

• Newborn screening + when?• increased immunoreactive trypsinogen (IRT)(pancreatic enzyme)•Confirmatory Sweat Chloride Test is?•=Gold standardPilocarpine iontoelectrophoresis >60 meq/L -- +•DNA analysis (Definitive diagnosis with?• 2 CFTR mutations•Most common defect is?•defect Delta 508, deletion of 3 bps leading to• absence of phenylalanine at codon 508.

Sudden infant death syndrome

SIDS

Definition SIDS – sudden unexplained death before

1 year of age in an otherwise healthy infant. The cause of death is unexplained despite a thorough investigation involving: Complete autopsy Death scene investigation Review of clinical history

Epidemiology 3rd leading cause of death in infants in ages 1

mos – 1 year. 2,300 infants die of SIDS every year in the U.S. There has been a steady decline in death from

SIDS with the implementation of Back to Sleep campaign that started in 1994.

SIDS rate has been constant since 2001. Many deaths that were previously classified as

SIDS are now being classified as other causes of death.

Risk Factors Male infants (occurs 3:2 compared to females) Prone and side sleeping position Maternal smoking during pregnancy Exposure to tobacco smoke Overheating Soft bedding Young maternal age Prematurity or low birth weight African American/American Indian

***Risk Reduction**** Strategies to decrease risk factors

Back to sleep for every sleep Use firm sleep surface Keep soft objects and loose bedding out of

crib Avoid tobacco smoke exposure during

pregnancy Room sharing without bed sharing is

recommended Avoid overheating

Pathophysiology

Failure of arousal mechanisms plays a big role in the pathway to death

Dysfunction of arousal and cardiorespiratory responses may be due to serotonin receptor abnormalities

Other causes may be polymorphisms in sodium channel gene that relates to prolonged QT syndrome

Certain genes seem to predispose infants to SIDS especially when they are exposed to smoking or prone position

Sleep position Evidence suggests that prone sleeping

results in altered autonomic control of the infant cardiovascular system during sleep Seen at 2-3 mos of age Get decreased cerebral oxygenation

Some parents are reluctant to try supine position because they fear infant will choke or aspirate

Bed Sharing AAP recommends infants share a room with

the parents, but not a bed Decreases risk of SIDS by 50% Adult beds are not designed for infant safety

May lead to accidental suffocation Entrapment Asphyxia

Highest incidence of SIDS is when bed sharing occurs during first 3 months of life and if they are born prematurely

Bed Sharing cont. Hazardous bed-sharing situations:

Infant <2 months Parents are smokers Infants placed on water beds or sofas

(soft surfaces) Pillows and blankets present Person sharing a bed is not a parent Person sharing a bed is intoxicated

Reasons for bed sharing Space/financial reasons Facilitates breastfeeding and bonding Environmental dangers:

Vermin Stray gunfire Random kidnappings

Parents believe parental vigilance at all times is best

Recommendation is to room share to maintain bonding and vigilance

Protective effects Breastfeeding

Studies have shown that SIDS risk halves when baby is breastfed

The risk decreases even more when the infant is exclusively breastfed

Breastfeeding decreases infectious diseases which is associated with SIDS

It is also easier to arouse infants from sleep that are breastfed than those that are bottle fed

Pacifiers AAP recommends pacifier use to decrease incidence

of SIDS

Protective effects cont. Crib and Bedding accessories:

Current recommendation is to place infant on firm surface Avoid bedding, pillows, blankets and use infant sleep

clothing Avoid bumper pads that may cause suffocation,

entrapment, and strangulation Parents normally use to them to avoid injuries Possibly for aesthetic reasons

Vaccinations Studies have shown that immunization decreases risk of

SIDS

Health Education Education about sleep position should be detailed

and include concerns of aspiration, choking, and infant comfort

Media messages that target child-bearing woman often depict infants in unsafe sleep positions and sleep environments (soft-bedding)

Important to be consistent in message Many parents question Back to Sleep campaign as

SIDS is said to have unknown cause so they don’t believe any changes in sleeping behavior could prevent death of infants

Other simply believe it is “God’s will”

QuestionAbnormalities in the receptor for which of the following neuropeptides have been identified in the brainstem of some infants with sudden infant death syndrome:

A. AcetylcholineB. EpinephrineC. GalaninD. SerotoninE. Vasoactive intestinal

peptide

Acety

lcholin

e

Epinephrine

Galanin

Seroto

nin

Vasoacti

ve inte

stinal p

e...

0% 0% 0%0%0%

Question: A mother of a 1-month-old infant comes in for a well-child visit. As you review the infant’s immunization schedule, she tells you that one of her friends’ children died of SIDS 48 hours after the infant received her 4-month diphtheria, pertussis, and tetanus vaccine. Of the following, which piece of information most accurately reflects current knowledge about immunizations and SIDS?

A. Infants who receive immunizations have a lower risk of SIDS

B. Infants who receive immunizations have the same risk of SIDS as infants who are not immunized

C. Infants who receive immunizations may have slightly higher risk of SIDS, but the benefit of the immunization far outweighs the risk

D. Only the 2-month diphtheria, pertussis, and tetanus vaccine has been associated with slightly increased risk of SIDS.

E. Infants at risk of SIDS should have their Haemophilus influenza vaccine series postponed until 12 months

Infants who re

ceive im

m...

Infants who re

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m...

Infants who re

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m...

Only the 2-m

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.

Infants at r

isk of S

IDS sh

...

0% 0% 0%0%0%

QuestionThe American Academy of Pediatrics Task Force on SIDS has recommended against parents sleeping in the same bed as their infants. According to the article, which of the following factors makes bed sharing especially hazardous?

A. Absence of blanketsB. Firm bedC. Infants age <3 monthsD. Maternal age <20 yearsE. Only 1 person sharing

the bed with the infant

Absence

of blankets

Firm bed

Infants age

<3 month

s

Mate

rnal a

ge <20 years

Only 1 person sh

aring t

..

0% 0% 0%0%0%

QuestionAn intervention recommended by authors to reduce the risk of infant SIDS is:

A. Avoid the use of pacifiers before bedtime

B. Home cardiorespiratory monitoring

C. Positioning the infant on the side

D. Sleeping in the same room as the infant

E. Swaddling the infant in a soft blanket

Avoid th

e use of p

acifiers.

..

Home card

ioresp

irato

ry...

Positioning t

he infant o

n...

Sleeping in th

e same ro

o...

Swaddlin

g the in

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a...

0% 0% 0%0%0%

Jog your memory slide

• Newborn screening + when?• increased immunoreactive trypsinogen (IRT)(pancreatic enzyme)•Confirmatory Sweat Chloride Test is?•=Gold standardPilocarpine iontoelectrophoresis >60 meq/L -- +•DNA analysis (Definitive diagnosis with?• 2 CFTR mutations•Most common defect is?•defect Delta 508, deletion of 3 bps leading to• absence of phenylalanine at codon 508.

•Treatment of Asthma?•B2 agonist/bronchdilators•Short acting for breakthrough symptoms

Ex. Albuterol (AKA internationally as salbutamol) Levalbuterol •Long acting -- used for maintenance in combination with inhaled corticosteroid (never without)

Ex . Salmeterol •Mechanism?•β2 receptors are activated on bronchial smooth muscle bronchodilation.• Stimulation of adenylate cyclase closing of calcium channels relaxation of smooth muscles

•Inhaled corticosteroids are first line therapy for?• Persistant asthma •Examples?•Mometasone•Fluticasone •Budesonide •Mechanism: inhibits the synthesis of cytokines and inactivates NF-κB that induces the production of TNF-α and other inflammatory agents)

References

Hill, Vanessa L., and Pamela R. Wood. "Asthma Epidemiology, Pathophysiology, and Initial Evaluation." Pediatrics in Review 30.9 (2014). Web. 4 Sept. 2014. <http://pedsinreview.aappublications.org/content/30/9/331>.

Marino, Bradley S., and Katie S. Fine. "Pulmonology." Blueprints Pediatrics. 5th ed. Lippincott Williams & Wilkins, 2009. 299-309. Print.

"Pathophysiology of Asthma." Wikipedia. 5 May 2014. Web. 6 Sept. 2014. <http://en.wikipedia.org/wiki/Pathophysiology_of_asthma>.

References Hill, Vanessa L., and Pamela R. Wood. ”Practical

Management of Asthma" Pediatrics in Review 30.9 (2014). Web. 4 Sept. 2014. <http://pedsinreview.aappublications.org/content/30/10/375>.

Marino, Bradley S., and Katie S. Fine. "Pulmonology." Blueprints Pediatrics. 5th ed. Lippincott Williams & Wilkins, 2009. 299-309. Print.

"Pathophysiology of Asthma." Wikipedia. 5 May 2014. Web. 6 Sept. 2014. <http://en.wikipedia.org/wiki/Pathophysiology_of_asthma>.

References1. Hauck FR, Thompson JM, Tanabe KO, Moon RY,

Vennemann MM. Breastfeeding and reduced risk of sudden infant death syndrome: a meta-analysis. Pediatrics. 2011; 128(1): 103-110

2. Moon RY, Fu LY. Sudden infant death syndrome. Peiatr Rev. 2007; 28(6): 209-214

3. Moon RY, Yang DC, Tanabe KO, Young HA, Hauck FR. Pacifier use and SIDS: evidence for a consistently reduced risk. Matern Child Health J. 2012;16(3):609-614

4. Tappin D, Ecob R Brooke H. Bedsharing, roomsharing, and sudden infant death syndrome in Scotland: a case-control study. J Pediatr. 2005; 147(1): 320

References 1. Montgomery GS, Howenstine M. Cystic

Fibrosis. Pediatrics in Review 2009; 30;302 2. Katkin, JP. Cystic Fibrosis: Genetics and

Pathogenesis. UpToDate. 2014. 3. Katkin, JP. Cystic Fibrosis: Clinical

Manifestations and diagnosis. UpToDate. 2014. 4. Marino, Bradley. Blueprints: Pediatrics 6th

edition 2013.

Seong J. Kim MS IV St. George’s University = croup and stridor Adnan Ismail, MS IV

Aamer javed, ms4 Sgu 8/1/2014

Snehali Patel, MSIV St. George’s University June 20th 2014

Adnan Ismail, MSIV Anousheh Afjei