WALTER REED JOURNAL CLUB

1. WALTER REED JOURNAL CLUB HOW TO USE A CLINICAL PRACTICE GUIDELINE (JAMA) Jennifer S. Kicker, MD 30 January 2007

2. Morning Clinic • 6mo male presents to clinic with “barking cough.” • 9mo male with paroxysms of cough and emesis. • 7yo female with known RAD presents with cough and wheezing. • 12yo male with remote history of URI has been “coughing since Thanksgiving.” • 15yo female with cough for past month, noticed by parents that only occurs after home from school.

3. AGENDA • Cough fast facts. • Article introduction. • Literature review of recommendations. • a.) Diagnostic approaches • b.) Etiology • c.) Treatment • Strength of evidence. • Applicable for our clinical practice?

4. COUGH “A rapid expulsion of air from the lungs typically in order to clear the lung airways of fluid, mucus, or irritating material. Often occurs in succession.” • Within the top 5 for number of doctor’s visits/yr • Money spent OTC/home remedies: ~$40 billion/yr • Lost time from work and school • Sleep disturbances

5. ARTICLE OF INTEREST Chang AB, Glomb WB. Guidelines for Evaluating Chronic Cough in Pediatrics: ACCP Evidence-Based Clinical Practice Guidelines. Chest 2006; 129: 260S-283S. Objective: To review relevant literature and present evidence-based guidelines to assist general and specialist medical practitioners in the evaluation and management of children who present with chronic cough.

6. INCLUSION CRITERIA • Articles on cough diagnosis, etiology, treatment, and complications were searched separately. • Children 0-14 years with cough >4 weeks duration. • English articles published Jan 1966 – Dec 2003. • Cochrane Register (CENTRAL), PubMed, EMBASE. • September 1 – December 5, 2003: abstracts identified and reviewed by single author. • 274 articles for full review. • Last search Cochrane: November 7, 2004. • Accepted for publication: December 5, 2004.

7. NOT SMALL ADULTS(CAUTION WITH EXTRAPOLATING ADULT LITERATURE) • Viruses responsible for common cold in adults may cause serious respiratory illness in kids. • Maturational differences in airway anatomy, respiratory musculature, chest wall structure. • Differences in medication response. • Medical history in young kids is limited by parental perception and availability. “Children should be managed according to the studies and guidelines for children (when available), because etiologic factors and treatments in children are sometimes different from those in adults.” (B)

8. DIAGNOSTIC APPROACHES “Children with chronic cough require careful and systematic evaluation for the presence of specific diagnostic indicators.” (E/A) “In children with chronic cough, the etiology should be defined and treatment should be etiologically based.” (E/A) “Children with chronic productive purulent cough should always be investigated to document the presence or absence of bronchiectasis and to identify underlying and treatable causes such as cystic fibrosis and immune deficiency.” (B) History and physical exam first: • Specific pointers suggestive of specific cough.

9. DIAGNOSTIC APPROACHES Pointers to the Presence of Specific Cough (Table 1) • Auscultatory findings, wheeze, crepitations • Cardiac abnormalities • Chest pain • Chest wall deformity • Digital clubbing, FTT (CF) • Neurodevelopmental (potential for aspiration) “In children with nonspecific cough, cough may spontaneously resolve, but children should be reevaluated for the emergence of specific etiologic pointers.” (B)

10. DIAGNOSTIC APPROACHES • Cough quality is suggestive of etiology, but no published studies on “dry cough” vs. “wet cough” • Most cough characteristics recognized as classical have not been formally evaluated. • 6mo male presents to clinic with “barkingcough.” • 9mo male with paroxysms of cough and emesis.

11. DIAGNOSTIC APPROACHES

12. DIAGNOSTIC APPROACHES • 12yo male with remote history of URI has been “coughing since Thanksgiving.” “Children with chronic cough should undergo, as a minimum, CXR and spirometry, if age appropriate.” (E/B) • CXR quick, readily attainable. • Spirometry reliably performed in kids > 6 yrs (often >3 yrs, with appropriate personnel).

13. DIAGNOSTIC APPROACHES Also considered: • Chest or sinus CT a.) HRCT as current gold standard for eval of small airway anatomy. b.) Lifetime cancer risk is age and dose dependent. c.) Single Chest CT scan ~ 5.8 mSv (CXR ~ 0.02 mSv, so = 300 CXRs). • Flexible bronchoscopy 1.) suspicion of airway abnormality. 2.) localized radiology changes. 3.) suspicion of inhaled foreign body. 4.) eval of aspiration lung disease. 5.) micro studies and lavage (BAL).

14. ETIOLOGY “In children with specific cough, further investigations may be warranted, except when asthma is the etiologic factor.” (E/B) • Cough is the most common presenting symptom in patients presenting to doctors in US and Australia. • Viral URIs, which also cause cough, are said to account for 80 percent of childhood asthma exacerbations. • 7yo female with known RAD presents with cough and wheezing.

15. ETIOLOGY Upper Airway Disorders and Cough • Upper airway cough syndrome (aka post-nasal drip) well documented in adults. • In children, relationship between nasal secretions and cough is more likely linked by common etiology (infection or inflammation). • Abnormal sinus radiographs found in 18-82% of asymptomatic children. • No RCTs on therapies for upper airway disorders in kids with improvement of nonspecific cough as outcome measurement.

16. ETIOLOGY GERD and Cough • PROOF that GERD causes chronic cough in kids is rare. • Infants often regurgitate, but few well infants cough with these episodes. • Available prospective studies of chronic cough in kids suggest that GERD is infrequently the SOLE cause.

17. ETIOLOGY Airway Lesions and Cough • Prevalence of airway lesions found in asymptomatic children is unknown. • Relationship of cough to airway lesion can only be postulated: • Airway malacia impedes clearance of secretions; potential for pneumonic process distal to lesion138

18. ETIOLOGY Environmental Pulmonary Toxicants • Increases susceptibility to respiratory infections143,144 • Increases coughing illnesses146,147 • Close association to tobacco smoke exposure, especially in association with asthma. • 15yo female with cough for past month, noticed by parents that only occurs after home from school. “In all children with cough, exacerbating factors such as ETS exposure should be determined and interventional options for the cessation of exposure advised and initiated.” (B)

19. ETIOLOGY Chronic Nocturnal Cough • Unreliability and inconsistency of reporting. • Often used as a direct indicator of asthma. • Community based study revealed only a third of children with isolated nocturnal cough had asthma. • No studies that objectively document that nocturnal cough is worse than daytime cough in uncontrolled asthmatics.

20. ETIOLOGY Respiratory Infections and Postinfectious Cough • Postviral cough refers to presence of cough after acute viral URI. Unstudied natural history beyond 25 days. • Re-infection (when not completely recovered) may result in appearance of prolonged coughing. • Total respiratory illnesses per person year ranges 5-8/yr (<4yrs) and 2.4-5/yr (10-14yrs). 40 • Classic infections (pertussis, Mycoplasma) typically cause cough with other symptoms, but consider antibiotics and vaccination as modifiers.

21. ETIOLOGY Psychogenic Cough • AKA habit cough, tic cough, psychogenic cough. • Behaviorial association. Inhalation of Foreign Body • Presentations usually acute, but chronic cough may be presenting symptom of missed FB inhalation. • Normal CXR does not exclude. • Specific history should be sought.

22. ETIOLOGY Parental Expectations • Parental expectations as well as the doctor’s perceptions (of said expectations) influences consulting rates and prescription use. 22,199,200 • Use of OTC meds and frequency of doctor’s visits were less likely with more highly educated mothers.201 • Parental concerns can be extreme and include fear of child choking and dying, SIDS, asthma attack, permanent chest damage. “In children with nonspecific cough, parental expectations should be determined, and the specific concerns of the parents should be sought and addressed.” (E/B)

23. TREATMENT OTC Cough Medications • Common unintentional ingestion in kids <5 years of age. • AAP advises against use of codeine and dextromethorphan for treating any type of cough. “In children with cough, cough suppressant and other OTC cough medicines should not be used as patients, especially young children, may experience significant morbidity and mortality.” (D)

24. TREATMENT Asthma Therapy • No evidence to support B2 agonists in children with acute cough but no evidence of airway obstruction.210 • No evidence to support anticholinergic agents. • Two RCTs on inhaled corticosteroids for treatment of chronic nonspecific cough in children. a.) Low dose ICS have been proven effective in the management of majority of cases of childhood asthma.219-221 b.) Authors recommend trial of pulmicort (budesonide) 400 ug/d equivalent dose, with reevaluation in 2-3 weeks. (B) c.) Cough may resolve due to ICS use, or by spontaneous resolution. • No RCTs on oral corticosteroids.

25. TREATMENT Antimicrobials • Two RCT: one with 23% kids coughing >30d and the second with mean duration of cough 21-28d. • In both studies, nasopharyngeal colonization showed predominance of Moraxella catarrhalis, and significant improvement was seen in treatment arm. • Cochrane review showed that 10d course of antibiotics reduces persistence of cough in short to medium term; NNT=8.

26. TREATMENT Antihistamines • For acute cough, antihistamine and decongestant combos were no more likely than placebo to reduce acute cough. • Recent RCT also showed diphenhydramine and dextromethorphan were no different than placebo in reducing nocturnal cough in kids. • In metaanalysis of antihistamine treatments for common cold, neither mono or combo antihistamine therapy was effective in reducing symptoms in kids. • No specific studies on cough >4 weeks. “In children who have started therapy with a medication, if the cough does not resolve during the medication trial within the expected response time, the medication should be withdrawn and other diagnoses considered.” (C)

27. RATING SCHEME “Children with chronic cough require careful and systematic evaluation for the presence of specific diagnostic indicators.” Level of evidence, expert opinion; benefit, substantial; grade of recommendation, E/A. Quality of Evidence • Good = evidence based on good RCTs or metaanalysis. • Fair = evidence based on other controlled trials or RCTs with minor flaws. • Low = evidence based on nonrandomized, case-control, or observational study. • Expert opinion = evidence based on consensus of the carefully selected panel of experts in the topic field.

28. RATING SCHEME “Children with chronic cough require careful and systematic evaluation for the presence of specific diagnostic indicators.” Level of evidence, expert opinion; benefit, substantial; grade of recommendation, E/A. Net Benefit • Substantial = Evidence of benefit that clearly exceeds the minimum clinically significant benefit, and evidence of little harm. • Intermediate = Clear evidence of benefit but with some evidence of harms. • Small/weak = Evidence of benefit that may not clearly exceed the minimum clinically significant benefit, or there is evidence of harm that substantially reduces the benefit. • None = no benefit or benefits=harm. • Conflicting = Evidence is inconsistent with regard to benefits or harms. • Negative = Expected harms exceed the expected benefits.

29. RATING SCHEME “Children with chronic cough require careful and systematic evaluation for the presence of specific diagnostic indicators.” Level of evidence, expert opinion; benefit, substantial; grade of recommendation, E/A. Strength of Recommendation • A = strong E/A = strong, expert opinion only • B = moderate E/B = mod, expert opinion only • C = weak E/C = weak, expert opinion only • D = negative E/D = neg, expert opinion only • I = no recommendation (inconclusive)

30. ARE THE RECOMMENDATIONS VALID? Were all important options and outcomes considered? • YES: Considered way more options than recommended Was an explicit and sensible process used to identify, select, and combine evidence? • YES: Defined a specific objective; defined inclusion criteria; conducted a comprehensive search

31. ARE THE RECOMMENDATIONS VALID? Was an explicit and sensible process used to consider the relative value of different outcomes? YES • International panel of 26 experts from 7 clinical specialties. • Many were ACCP members, but other medical societies represented. • Quality of evidence is rated on study design. • Net benefit is based on estimated benefit to the specific patient population, not for an individual patient. • With insufficient evidence, the panel used informal group consensus techniques to reach an expert opinion.

32. ARE THE RECOMMENDATIONS VALID? Is the guideline likely to account for important recent developments? YES • 203 of 274 articles were published after 1995 • Few articles cited for things currently being published at time of printing. • Date of most recent evidence considered (last search) November 7, 2004. • Accepted for publication: December 5, 2004.

33. ARE THE RECOMMENDATIONS VALID? Has the guideline been subjected to peer review and testing? • YES: internal and external peer review • Following final revisions, each section of the guideline was reviewed/approved by: 1.) Clinical Pulmonary Medicine 2.) Respiratory are 3.) Pediatric Chest Medicine 4.) Environmental and Occupational and Airways Disorders Networks of the ACCP 5.) ACCP Health and Science Policy Committee 6.) ACCP Board of Regents

34. WHAT ARE THE RECOMMENDATIONS? Are practical, clinically important, recommendations made? • YES, BUT recommendations made were conservative, many vague, blanket statements. How strong are the recommendations? – FAIR/WEAK • Only 4 RCTs available for inclusion. • Much heterogeneity among reviewed studies looking at the same topic. • Half (6/13) of the recommendations are based on expert opinion only.

35. WHAT ARE THE RECOMMENDATIONS? What is the impact of uncertainty associated with the evidence and values used in the guidelines? • As compared to adult literature, uncertainty exists regarding similar outcomes (to treatment strategy) in children. • Authors free acknowledge the paucity of pediatric studies. • Actual outcomes in well designed research may be much greater, or much less, than their best estimate.

36. WILL RECOMMENDATIONS HELP PATIENT CARE • YES • This guideline is directed towards primary care. • Services offered in the subspecialty arena are in the context of a primary care referral after initial evaluation.

37. WILL RECOMMENDATIONS HELP PATIENT CARE MAYBE • Not a lot of new info here. • Reinforces careful and methodic evaluation of chronic cough. • Rule out serious pathology. • Opportunity to counsel parents regarding OTCs. • Recognize parental expectations and address concerns. • Describes a similar patient population: cough >4 weeks is not rare.

38. QUESTIONS?