Common Causes of Airway Distress

Educational Objectives

The goal of this program is to improve the clinical diagnosis and management of bronchiectasis, bronchiolitis, and croup. After hearing and assimilating this program, the clinician will be better able to:

1.   Recognize patients suffering from bronchiectasis-related airway distress.

2.   Recommend therapies, medications, and medical devices that can improve quality of life in patients with cystic fibrosis (CF) and non-CF bronchiectasis.

3.   Distinguish allergic bronchopulmonary aspergillosis from asthma and other causes of bronchiectasis.

4.   Assess patients for bronchiolitis and provide appropriate management.

5.   Provide supportive care to alleviate symptoms associated with croup.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Flume receives grant support from Novartis, MPEX, and Bayer, and is on the Speakers’ Bureau for Pfizer. Dr. Marmor and the planning committee reported nothing to disclose. In his lecture, Dr. Flume presents information related to off-label or inves­tigational use of a therapy, product, or device.

Acknowledgments

Dr. Flume was recorded at 5th Annual Conference on Medical Dilemmas in Primary Care, held December 19-21, 2008, in New York, NY, and sponsored by the Southern Medical Association. Dr. Marmor was recorded at Annual Review in Family Medicine, held April 19-21, 2009, in San Francisco, CA, and sponsored by the Department of Family and Community Medicine of the Uni­versity of California, San Francisco, School of Medicine. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Bronchiectasis: No Longer an Orphan Disease

Patrick Flume, MD, Professor of Medicine and Pediatrics, Medical University of South Carolina, Charleston

Background: classified orphan disease by Food and Drug Administration; occurs predominantly in older patients; higher rate of diagnosis in women (thin women of advanced age at highest risk); not considered rare disease; fre­quently unrecognized; smaller degrees of bronchiectasis (visible on computed tomography [CT]) increasingly rec­ognized as cause of symptoms; high per capita costs; predominantly treated in inpatient setting; characterized by abnormally dilated airways; multiple etiologies; easily detected due to presence of large dilated airways and cystic changes; radiography  —  difficulty distinguishing between airway tissue and adherent phlegm obscures assessment of airway size on CT; healthy airways typically smaller in diameter than attached blood vessels (useful size refer­ence; equal size or larger indicates bronchiectasis)

Pathophysiology of cystic fibrosis (CF): similar pathway could account for most cases of bronchiectasis; CF  —genetic defect causing abnormalities in lung cilia (primary ciliary dyskinesia) or other altered bronchial dynamics; malformed cystic fibrosis transmembrane conductance regulator (CFTR) protein interferes with chloride regula­tion; chloride accumulation causes lung tissue to swell, which creates shallow airway surface depth and prevents cilia from standing erect; impaired ciliary function causes abnormal clearance of mucus; hypertonic saline may in­crease depth of airway surface liquid and improve clearance of mucus; abnormal clearance promotes chronic or re­current infections; patients with CF lose ability to fend off commonly aspirated bacteria; inflammation resulting from infections interferes with ciliary function and produces pathology, thereby further reducing airway clearance and perpetuating underlying pathology; immune impairment (eg, immmunoglobulin deficiency, T-cell–mediated deficiencies) or injury may cause similar chain of events

Pathophysiology of bronchiectasis: must differentiate between focal (single lobe or lung segment) and diffuse (bi­lateral) disease

Focal disease: patients may report serious pneumonia earlier in life (typically bacterial, influenza-related, or myco­bacterial [eg, tuberculosis]); airway obstruction (foreign body)  —  may mimic intractable asthma with severe coughing; bronchial stricture  —  high concentration of lymph nodes surrounding airway of right middle lobe may impair clearance; bronchial masses (rare)

Diffuse disease: most common; causes include  —  postinfection pathologies; congenital syndromes (eg, CF, primary ciliary dyskinesias); immunodeficiency states, eg, immunoglobulin deficiency (uncommon), HIV (causes lym­phocytic interstitial pneumonia in pediatric patients and mimics CF bronchiectasis); and immune-mediated dis­ease (eg, allergic bronchopulmonary aspergillosis [ABPA], rheumatoid arthritis, Sjögren's syndrome; recurrent aspiration (common; predominantly occurs in lower lobes posteriorly and bilaterally); etiology undetermined in 53% of patients

Management: clearing airways should receive top priority; airway clearance effective, but no therapy shown superior to any other; find therapy that works best for individual patient; percussion and postural drainage  —  percussion with cupped hand produces pressure wave; relaxation (after compression) produces volume and airflow changes capable of dislodging secretions; gravity alone not sufficient to clear airways; vibratory positive expiratory pres­sure (PEP) therapy system (Acapella) and high-frequency chest wall oscillation vest (The Vest)  —  highly portable; vest compresses and relaxes lungs in oscillatory manner; intrapulmonary percussive ventilation  —  inflates and re­laxes lung in oscillatory manner (allows aerosolized therapy as additional benefit); bronchodilators  —  may provide limited benefits; dornase alfa (Pulmozyme)  —  indicated for CF; no improvement of lung function in studies of non-CF bronchiectasis (possibly due to lower levels of secretion); speaker uses for patients with copious secretions who show insufficient response to other therapies; costs »$1000/mo; hypertonic saline  —increasing concentration of salt rapidly improves airway clearance; »7% saline used (highest tolerable concentration); mannitol  —  studies on­going; when inhaled, mannitol acts as osmotic agent capable of pulling fluid into airways (enhances clearance of mucus); in non-CF bronchiectasis, mannitol may alleviate symptoms by increasing airway surface depth; diagnos­tic testing  —  limit to conditions amenable to intervention (eg, ABPA, aspiration, immunoglobulin deficiency, a1-antitrypsin deficiency)

Allergic bronchopulmonary aspergillosis: allergic asthma with bronchiectasis; patients show allergic reaction to common fungus (Aspergillus); treated with steroids and antifungal therapy (less common); omalizumab (Xolair) found beneficial in case reports; ABPA presents with large central bronchiectasis and copious secretions (often with brown plugs); presence of Aspergillus in sputum not major criterion for diagnosis; diagnosis primarily indi­cated by high levels of Ig E (extreme values >5000 kU/L reported); elevated antibodies to Aspergillus observed; produces immediate skin reaction to Aspergillus antigen (in-office test); secondary tests  —  eosinophilia may indi­cate ABPA; measuring infiltrates not useful (transient infiltrates typical with bronchiectasis); 8% of CF patients have ABPA (compared to 1% of normal population); speaker recommends evaluating all patients with diffuse bron­chiectasis for ABPA

Bronchiectasis: eradication of infections not possible; antimicrobial strategy should focus on treating exacerbations and on maintenance regimens; microbiology  —  Pseudomonas aeruginosa predominant in adults with CF; 70% to 80% of patients show P aeruginosa in cultures; Staphylococcus aureus infection rates increasing (attributed to in­creased screening rather than increased prevalence); infection patterns similar in non-CF bronchiectasis, but with significant occurrences of Haemophilus influenzae; improvements in molecular diagnosis revealed greater numbers of anaerobic bacteria than previously estimated (role in pathogenesis undetermined); fungi  —Candida nearly uni­versal in patients with bronchiectasis; Aspergillus significantly common; role in pathogenesis undetermined (ex­ceptin ABPA); mycobacteria  —  dramatic increases in prevalence and recognition reported; typically Mycobacterium avium and Mycobacterium abscessus; prevalence increases in older patients; study of non-CF bronchiectasis found mycobacteria in cultures from 45% of patients; treatment recommended only with indicators of disease (eg, clinical symptoms, microbiologic features, radiographic changes); patients typically coughing; speaker does not recommend routine biopsies; treating exacerbations requires knowledge of microbiology; recur­rent exacerbations  —  traditional approaches apply rotational antibiotic regimens (not recommended; does not tar­get pathogens present in cultures); acute exacerbations  —  clinical features include worsening of symptoms, but may or may not include fevers, chest pain, or infiltrates;  repeat cultures before determining treatment

Treatment: Pseudomonas  —  speaker asserts dual therapy may not be necessary in all patients; inhaled antibiotics  —average concentration of 1200 µg/g of sputum targeted when administering tobramycin (final concentrations vary significantly between patients); peak serum concentration <1 µg/mL; greater concentration at site of infection pro­duces greater efficacy with lower drug concentrations (greater safety); tobramycin inhalation solution  —  received grade A recommendation for CF patients with moderate to severe disease and B recommendation for CF patients with normal lung function or mild disease plus Pseudomonas infection; in study of 74 patients with non-CF bron­chiectasis and Pseudomonas, tobramycin for 4 wk had no effect on lung function; macrolide antibiotics  —  not indi­cated for bronchiectasis; not recommended against Pseudomonas; demonstrated lethal effects against bacteria, reductions in Pseudomonas biofilms, and inhibition of virulence factors; indicated in H influenzae infection; signif­icant antiinflammatory effects (eg, reduced neutrophil recruitment, reduced cytokines, inhibited neutrophil migra­tion); long-term macrolide therapy received B grade recommendation for CF; speaker reports “great success” despite lack of indication; small pilot study of patients with idiopathic bronchiectasis given 500 mg azithromycin twice daily reported improvements in forced expiratory volume in 1 sec (FEV₁) and decreased sputum volume; studies to determine ideal dosage ongoing, but all dosages evaluated appear efficacious; high incidence of nontu­berculous mycobacteria (NTM) observed in bronchiectasis patients (requires macrolide therapy); long-term macro­lide therapy not recommended for patients with NTM; macrolide-resistant S aureus  —prevalence increasing; single study reported rise to 100% (from 10%) of patients; no effects on outcome or treatment; bleeding  —  speaker en­courages patients to report any blood in sputum; embolization highly successful at stopping bleeding; speaker rec­ommends surgery only as last resort

Conclusions: patients who appear to have chronic bronchitis with multiple exacerbations should receive high-resolu­tion CT and special consideration for bronchiectasis

Bronchiolitis and Croup

Andrea Marmor, MD, MSEd, Assistant Clinical Professor of Pediatrics, University of California, San Fran­cisco, School of Medicine

Diagnosing bronchiolitis: American Academy of Pediatricians (AAP) guidelines (2006)  —  strictly recommend clini­cal diagnosis (as predictive as microbiologic diagnosis; routine diagnostic tests (eg, chest x-rays, microbiologic testing) not recommended (data show no effect on prognosis, outcome, or treatment; tests recommended only when results may affect treatment); respiratory syncytial virus (RSV)  —  premature infants with gestational age <46 wk and full-term infants <6 wk old at risk for apnea caused by RSV; young infants with RSV may be asymptomatic and may require microbiologic diagnosis (admit overnight to observe for apnea); fever with unknown source  —bronchiolitis may be safely diagnosed as cause of fever without testing for RSV (confirmed by multiple studies); speaker recommends checking all febrile infants <3 mo of age for urinary tract infection

Treatment of bronchiolitis: supportive care  —  oxygen; fluids; nasal suctioning (critical; removing upper airway ob­struction may significantly reduce respiratory distress); albuterol  —  long history of use in bronchiolitis; multiple studies found no efficacy; patients with smooth muscle involvement may still show improvement; AAP recom­mends single-dose trial of albuterol or racemic epinephrine (supported by stronger evidence); corticosteroids  —  large randomized controlled trial (RCT) showed no efficacy; »15% of patients presenting with bronchiolitis also have asthma (compared to 5%-6% of baseline population); patients with both conditions may respond; routine use not recommended; risk factors for asthma  —  strong family history; atopy (eg, eczema, allergies); previous episodes of wheezing; response to albuterol; studies show no association between corticosteroids and worsening of bronchi­olitis; nebulized hypertonic saline  —  thought to dehydrate secretions; studies typically combine with bronchodila­tor (shown superior to bronchodilator alone); saline may act as bronchial irritant (can worsen bronchospasms); speaker recommends combining with bronchodilator

Hospital admission: AAP guidelines  —  recommend supplemental oxygen (in hospital or home) for patients with O₂ saturation persistently <90%; ideal O₂ saturation level uncertain (data ambiguous); high altitude study  —  children with bronchiolitis randomized to receive inpatient admission plus O₂ or receive O₂ at home; no difference in out­comes between groups; disposition changed in 20% of patients over 8 hr of observation; speaker recommends ob­serving all patients (if possible) before deciding whether to admit

Croup: seasonal; affects 1% to 6% of children (typically during second year of life); clinical diagnosis (requires no testing or radiography); racemic epinephrine  —  proven treatment; produces immediate improvement; mist therapy  —  parents may take child into any steam-filled area; standard therapy for mild croup; never demonstrated superior to placebo in RCTs (contradicts common clinical experience); now excluded from treatment guidelines; speaker recommends attempting due to relative harmlessness (but only in mild cases); corticosteroids  —  proven ef­ficacious in moderate and severe croup; dexamethasone most often prescribed (standard single dose of 0.6 mg/kg of body weight); both dexamethasone metabolism and croup typically last 36 to 72 hr; oral administration; no ad­vantage found with intravenous (IV) or intramuscular dosing; IV formulation may be administered orally for con­centrated dosing (pH neutral; tasteless; inert; well-tolerated); corticosteroids did not affect most outcome measures in mild croup, but may decrease duration and severity of symptoms in patients kept awake by coughing; indications for racemic epinephrine  —  stridor at rest; severe upper airway obstruction; retractions; difficulty feeding; no evi­dence for admission after administration; patients should remain under observation for »2 hr; all patients receiving racemic epinephrine receive single dose of corticosteroids to manage inflammation

Alternative causes of airway distress: noninfectious causes  —foreign body (always consider in young children); anaphylaxis (symptoms may be subtle); epiglottitis  —  incidence significantly declined since introduction of vac­cine against H influenzae; now more common in adults; microbiology has shifted from predominantly H influenzae to predominantly S aureus and Streptococcus pneumoniae; children appear seriously ill (eg, toxic, rapid progres­sion of respiratory distress, stridor, “tripoding” [leaning forward], drooling); lateral neck film confirms diagnosis; examination with laryngoscope contraindicated; treated with airway support and antibiotics; tracheitis  —  most common cause of life-threatening upper airway infection in children; predominantly caused by S aureus; difficult to diagnose (no particular radiographic findings or examination signs); may mimic severe croup; treated with air­way support and antibiotics; retropharyngeal abscess  —typically spreads from infections in nearby structures (eg, group A streptococcal infection, staphylococcal infection, Streptococcus viridans infection of mouth); patients typ­ically avoid moving neck (extension causes most pain); classic findings on lateral neck film; treated with airway support and antibiotics; multiple studies have shown medical management sufficient (surgery unnecessary)

Suggested Reading

Agarwal R et al: Allergic bronchopulmonary aspergillosis: lessons from 126 patients attending a chest clinic in north India. Chest 130:442, 2006; Bajaj L et al: A randomized trial of home oxygen therapy from the emergency department for acute bronchiolitis. Pe­diatrics 117:633, 2006; Corneli HM et al: A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis. New Eng­land Journal of Medicine 351:357, 2007; Cymbala AA et al: The disease-modifying effects of twice-weekly oral azithromycin in patients with bronchiectasis. Treatments in Respiratory Medicine 4:117, 2005; Daviskas E et al: Effect of increasing doses of manni­tol on mucus clearance in patients with bronchiectasis. European Respiratory Journal 31:765, 2008; Flume PA et al: Cystic Fibrosis pulmonary guidelines. American Journal of Respiratory and Critical Care Medicine 176:957, 2007; Ilowite J et al: Bronchiectasis: new findings in the pathogenesis and treatment of this disease. Current Opinion in Infectious Disease 21:163, 2008; Leung AK et al: Respiratory syncytial virus bronchiolitis. Journal of the National Medical Association 97:1708, 2005; Parr DG et al: Significance of bronchiectasis in patients with a1-antitrypsin deficiency. American Journal of Respiratory and Critical Care Medicine 178:208, 2008; Scolnik D et al: Controlled delivery of high vs low humidity vs mist therapy for croup in emergency departments: a random­ized controlled trial. The Journal of the American Medical Association 295:1274, 2006; Tal G et al: Hypertonic saline/epinephrine treatment in hospitalized infants with viral bronchiolitis reduces hospitalization stay: 2 years experience. The Israel Medical Associa­tion Journal 8:169, 2006; Wyecker D et al: Prevalence and economic burden of bronchiectasis. Clinical Pulmonary Medicine 12:205, 2005