Chronic cough4 09


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  • Few things to note: Valsalva requires closed airway, therefore pt with trash or paralyzed cords can’t cough very well
    Inspiratory muscles= diaphragm & accessories
    Expiratory muscles= intercostals and abdominals
    Expiratory blast requires functional exp muscles, C6 quad loose this ability and have much less effective cough
    Exp blast can reach 500mph!
  • Irwin and co-workers retested their algorithm in 1990, and again confirmed that PND, Asthma and GER accounted for the majority of patients.
    Even in latest consensus guideline review of 11 studies worldwide—UACS, asthma and GERD account for 2/3 of all dx. The biggest differences are in the incidence of “post-infectious” and non-asthmatic eosinophillic bronchitis.
    Misc: bronchogenic CA in 2, chf, sarcoid, Zenker’s diverticulum, ACE inhibitor.
    In a follow-up study, also found same distribution in elderly x increased number with ACE induced cough. (PND, asthma and GER = 85%)
  • Sx: chronic cough, head aches, PND, facial discomfort, decreased smell,
    Organisms: often anaerobic, and lesser prevalence of aeribes and faculative orgs: S. aureus,, s. epi, grams negs.
    Etiology: probably related to recurrent acute sinus infections then develop chonic tissue inflammation associated with makred sunuts mucosal thickening and nasal polyps.
    RX: Augmentin, Floxins,
    If no response: consider culture. Can be caused by fungi (especially aspergillous), TB. Principles: Prolonged antibiotic therapy for 3 to 6 weeks with appropriately selected agent (similar to those used for acute infections). First Line: Amoxicillin/Clavulanate (Augmentin) 875mg po bid x 3-6 weeks Alternatives: Clindamycin (Cleocin) 300 mg po tid x 3-6 weeks Cefuroxime axetil (Ceftin) 500mg PO bid x 3-6 weeks Cefprozil (Cefzil) 500mg PO bid x 3-6 weeks Clarithromycin (Biaxin) 500mg PO bid x 3-6 weeks Gatifloxacin (Tequin) 400mg PO qd x 3-6 weeks Levofloxacin (Levaquin) 500mg PO qd x 3-6 weeks Moxifloxacin (Avelox) 400mg PO qd x 3-6 weeks
  • SLIDE: Positive MCC
    slide: cough variant asthma
  • Cough variant asthma first recognized by McFadden, Corrao. These are patients whose primary manifestation of asthma is cough. Do not have wheezes. By definition have normal spirometry @ baseline, but + methacholine challenge, when tested.
    Cough is nonproductive, repetitive, occurs day and night, and is exacerbated by excercise, cold air or URI. Look for + family hx, seasonal variation
    Methacholine is expensive, exhausting.
    I ‘ll only briefly mention CVA to this audience, because I think we’re all faminilar with it.
    The most interesting aspect of CVA as it relates to intractable cough, I think, is the mechanism. We’ve talked about the cough receptors and neurophysiology. Cough receptors are more prevalent in the proximal airways, and decrease in density as the airways get smaller. It is thought that in CVA the inflammation is more prominent in the proximal airways where it causes cough, and less so distally, where the inflam and narrowing would cause wheezing and dyspnea.
    Treatment is the same for cough variant asthma as for typical asthma
  • Both—submucosal eosinophilia and thickening of the basement membrane and limina reticularis
    Only asthma had mast cells in bundles of airway smooth muscle.
    This picture shows an airway bx of asthma
    Figure 2. Bronchial-Biopsy Specimens from Subjects with Asthma. Panel A shows epithelium, submucosa, and smooth muscle with mast cells (arrows) infiltrating the airway smooth muscle (x100). Panel B shows mast cells within the airway smooth muscle (hematoxylin, x400).
  • NOW WHAT? Now you take the history again. This time she recalled some episodes of heart burn. Also admitted that she’d had an endoscopy a few years ago, and had esophagitis.
    Important point: 75% of patients with GERD-induced cough do not have heartburn. Tip of the iceberg.
    Many patients have more than one cause.
  • Nissen fundoplication
  • In the past, there has been the debate: reflex vs. aspiration.
    Pts with aspiration clearly cough, but usually easy to dx.
    Clear now that cough can be mediated by reflex:
    This study by Ing et al confirms this....highly selected group of patients with no other cause for cough x GERD.
    DATA SLIDE: coughs c saline & HCL—On the right side, coughs with just saline. On the left, cough with HCl. As you can see patients signif. More likely to cough with either. Note 4 of 12 control patients that cough with HCl.
    DATA SLIDE: This slide shows what happen when they tried blocking the cough reflex with lidocaine(general anesthetic) in the esophagus. Ipratropium (anticholinergic) did not block the cough.
    DATA SLIDE: Inhaled ipratropium does block the reflex—from this study, ipratropium is best inhaler to use in patients with GERD-induced cough.
    To further complicate: of control subjects without demonstated spontaneous GERD, only 4/12 coughed when they had acid instilled into their distal esophagus. So it looks like you need two factors for GERD to cause cough: spontaneous GERD and the propensity to cough.
  • Importantly—some of the patients still coughed just with normal saline. Significant in that bland reflux can still be a cause of cough.
  • What about therapy of cough due to reflux? I am not talking here about pts with clear PUD etc.
    All patients should have conservative measures instituted: including HOB, caffeine, no eating before bed. Low fat diet had been shown to be effective, but difficult to follow. Dr.. Irwin’s diet.....I have one pt with persistent reflux: “I’d rather cough”
    Proton pump inhibitor-- more effective than H2
    need high dose and bid. Best if 2nd dose given just before evening meal
    How long is controversial—MOST patients will respond in 2 weeks, but some say need to rx up to 6 mos!!
    Usually in combo with motility therapy
    Cisapride action, need qid!
    Both drugs are very expensive, and need to use for a long time. I do not know of studies of looking at cost-effectiveness of empiric trial vs. pH probe.
    I do probe
    Motility therapy: Important to consider—many patients show delayed acid clearing from stomach.
    Omeprazole H+K+ATPase inhibitor-binds to pump, therefore inhibits all acid stimulation
  • 46 yo MIT Secretary--lots of student contact
    3 wks severe cough
    Followed mild “cold”--only runny nose, mildy sick, cough started about 3 or 4 days into it
    Cannot talk, sleep really debilitated
    Cough comes in “fits”--I think this helps point me toward a diagnosis of reflux, asthma or this entity.
    Otherwise very healthy
  • Friday, June 8, 2007
    Cape hospital hunts for whooping cough exposure
    By Stephen Smith, Globe staff
    Cape Cod Hospital embarked on a massive hunt to track down about 1,000 patients, relatives, and staff members who might have been exposed to whooping cough by workers in a cancer clinic.
    The Boston Globe
  • Most cases now under age one, >15 years. Many cases in adults.
    In Massachusetts, 92% of cases in adolescents and adults.
    Pathogenesis of cough related to toxins: dermatonecrotic toxin, and tracheal cytotoxin--so it kills cells lning the upper airway. By the time the patient is symptomatic, some damage has been done and this is why abx may not change course of cough.
    Whoop is uncommon in adults. Caused on inspiration after coughing fit, and because adult airways are larger, don’t get whooping sound.
    Chicago outbreak: 26% of adults presenting with a week or more of cough showed serological evidence of recent infection. Range in length cough was 2-130 days.. No clinical diff betw pertussis, nonpertussis
    Difficult diagnosis--report from JAMA re outbreak in Chicago in 1993 was that cx + in 1/10 adults with serologic evidence of recent infection. Also, no difference in clinical presentation between those with and without laboratory evidence of infection.
    Another study from Kaiser in California not during an outbreak: 12% of all adults presenting with cough x 2 weeks.
    Dx: if within 14d, culture of nasopharyngeal secretions-(Ca+alginate swabs, special media, otherwise by titre
    Treat with Erythro, Clarithro, TCN, Bactrim, choramphenicol. We have all undoubtedly treated it without knowing.
    Clinical features: starts out like the common cold, slight temp, running nose. 2nd week cough is paroxysmal, but no fever or systemic symptoms or signs. Absolute lymphocytosis is common. Post-tussive whoop and vomiting are common.
    Prophylaxis—macrolide abx, or Bactrim for those allergic to macrolides.
  • Treat with Erythro, Clarithro, TCN, Bactrim, choramphenicol. We have all undoubtedly treated it without knowing
    Serology: (anti-pertussis toxin)*
    Massachusetts lab: + up to 56 days
    Serology > 20 mcg
    Culture not sensitive
    Direct fluorescent antibody (DFA)
    Polymerase chain reaction (PCR)
    Serology: (anti-pertussis toxin)*
    Massachusetts lab: + up to 56 days
    Serology > 20 mcg
  • N=28. Patient all with chronic cough after URI. Full eval for other causes.
    PVVN-has been described in various ways in literature. Mostly with a Bell’s palsy-like paralysis of vocal fold (recurrent laryngeal.) Also described as a “sensory neuropathy”—almost like a parathesia after shingles.
  • Chronic cough4 09

    1. 1. Chronic Cough Barbara A. Cockrill, MD Massachusetts General Hospital Harvard Medical School
    2. 2. Cough • Vital protective mechanism • Four steps: – – – – inspiratory gasp Valsalva maneuver expiratory blast as cords abduct post-tussive prolonged inspiration
    3. 3. Chronic Cough • Common things are common • Patients who do not respond frequently have more than one cause • GERD causes cough. • Post-infectious cough is common
    4. 4. Causes of Cough ACCP Chest 2006 100 80 70 60 50 41 40 40 24 21 20 30 5 4 5 20 10 mi sc CB PI EB Br CB on ch iec t Mi sc As th m a GE RD UA CS ER D 0 0 UA C/ As /G 60 80 Irwin 1990
    5. 5. Number of causes of cough Patients % 100 75 73 50 20 25 7 0 1 2 Number of Causes of Cough Smyrnios et al Arch Intern Med 1998 158:1222 3
    6. 6. Chronic Cough: D.A. • • • • 55 yo school secretary C/O cough for 3 years Non-smoker Cough: – Often productive, wax/wane – Better c abx, but comes back – “no better” with asthma meds – worst in AM
    7. 7. Chronic Cough: D.A. • • • • • Nasal voice, afebrile, looks well Mild “cobblestoning” No facial tenderness normal heart and lungs normal spirometry
    8. 8. Chronic Sinusitis • • • Often paucity of symptoms Often improvement with antibiotics Dx: Clinical & Sinus CT scan
    9. 9. Chronic Sinusitis • Evaluation – Allergies – Immunological • Rx: • • • • • • Prolonged antibiotics (3-6 weeks) Immunotherapy Topical steroids antihistamine/decongestants Sinus irrigation Consider surgical evaluation
    10. 10. Chronic Cough: The Computer Programmer • 35 yo woman • Yearly cough – starts only after a “cold” in fall or winter,lasts until mid-summer – Severe coughing FITS – goes away by itself – has happened last 4 years. • Tried “everything”
    11. 11. Chronic Cough: The Computer Programmer • Denies: wheezes, PND sx, allergies heartburn, aspiration • No: pets, exposures, current meds • Family hx negative • PMH: negative • Physical exam and CXR normal • Normal spirometry, no bronchdilator effect • “I can’t take it any longer!”
    12. 12. Methacholine Challenge Testing
    13. 13. Cough Variant Asthma • • • • Cough is sole symptom Spirometry is normal Up to 25% of asthmatics Diagnosis: – Positive methacholine challenge – Response to therapy • Mechanism
    14. 14. Non-asthmatic Eosinophilic Bronchitis • Eosinophilic airway inflammation WITHOUT variable airflow obstruction • Responds to inhaled corticosteroids • Dx = – sputum or BAL eosinphilia – Lack of variable airflow obstuction – Response to corticosteroids
    15. 15. Asthma vs. NAEB: Different localization Mast cells Brightling et. Al. NEJM 2002;346:1699
    16. 16. Chronic Cough: The Computer Programmer • Aggressive asthma regimen x 4 weeks • “I am only one iota better.......” • NOW WHAT?!
    17. 17. Reflux Esophagitis
    18. 18. Esophageal-tracheobronchial cough reflex & GERD • 22 pts with reflux & cough, 12 controls • Instilled acid into distal esophagus • Looked at effects of – – – Esophageal lidocaine Esophageal ipratropium Inhaled ipratropium Ing et al 1994
    19. 19. ⇑ cough in patients (p<.0001) Ing 1994
    20. 20. Cough blocked by esophageal lidocaine, not by esophageal ipratroprium
    21. 21. Cough blocked by esophageal lidocaine, not by esophageal ipratroprium Instillation of lidocaine before instillation of HCl Ing 1994
    22. 22. Cough was blocked by INHALED ipratropium Ing 1994
    23. 23. Cough blocked by INHALED ipratropium Ing 1994
    24. 24. Cough and Reflux Cough GERD causes cough & lowers cough threshold ⇑ Reflux ⇑ abdominal pressure
    25. 25. Lifestyle Changes for GERD • Stop smoking • Avoid alcohol • Lose weight • Elevate HOB • Small meals • • • • Avoid fatty/acidic foods High protein/low fat diet Avoid caffeine Avoid – tight clothes – eating < 4 hrs pre-bed – Recumbency 3 hrs post
    26. 26. Medications that ⇓ LES tone • • • • • • Theophylline Progesterone Alpha-adrenergic antagonists Beta-adrenergic antagonists Calcium channel blockers Nitrates
    27. 27. Cough & GERD: treatment • Conservative measures • Antacid therapy: – Proton pump inhibitor (high dose) – H2 blockers less effective • Motility therapy: – Metoclopromide (Cisapride) • Surgery is last resort
    28. 28. Cough & GERD • May be silent (up to 75%) • May complicate other causes • Diagnosis can be difficult – pH probe vs. therapeutic trial • • • Treatment must be aggressive Bland reflux can still cause cough Surgery effective in some patients
    29. 29. Chronic cough: J.B. • • • • • • • 46 yo woman Secretary in College Infirmary 3 wks severe cough Followed mild “cold” Cannot talk, sleep Cough comes in “fits” Otherwise very healthy
    30. 30. “The art of medicine is amusing the patient until Nature cures the disease.” -Voltaire
    31. 31. The Boston Globe Friday, June 8, 2007 Cape hospital hunts for whooping cough exposure By Stephen Smith, Globe staff Cape Cod Hospital embarked on a massive hunt to track down about 1,000 patients, relatives, and staff members who might have been exposed to whooping cough by workers in a cancer clinic.
    32. 32. B. pertussis “The hundred Day Cough” • Bordatella pertussis, parapertussis • Immunity wanes 12 yrs after vaccine • Phases: – catarrhal, paroxysmal, convalescent • Abx ⇓ infectivity, no effect on cough • Prophylaxis
    33. 33. Trachea: effect of pertussis
    34. 34. Why diagnose pertussis? • Treatment: – does not ⇓ paroxysmal phase – does ⇓ infectivity • • • Prophylaxis To reassure patient Minimize further work-up
    35. 35. New CDC Guideline Dec. 2006 • All adults should receive Tdap x 1 •Tetanus •Diphtheria •Pertussis
    36. 36. Post-infectious cough: Vagal neuropathy?? Jeyakumar et. al. Laryngoscope 116: 2108, 2006
    37. 37. Chronic Cough: Conclusions • Common things are STILL common • Many patients have > 1 cause • Most patients respond to therapy
    38. 38. Thank you