Common and Uncommon Causes of Chronic Cough Douglas B. Hornick, MD Professor Division of Pulmonary, Critical Care, and Occupational Medicine University of Iowa

Objectives Differentiate acute from chronic cough Review the most common causes as well as uncommon causes of chronic cough Discuss treatment strategies

Great Reference Irwin RS, et al: Diagnosis & Management of Cough: ACCP Evidence-based Clinical Practice Guidelines. Chest 2006; 129:1S-292S.

How do you define chronic cough?

Definitions & Epidemiology Cough persisting > 3 weeks Acute = up to 3 weeks Subacute = 3-8 weeks Chronic = >8 weeks 2008: Most common symptom among outpatients (>26 million office visits US) ~40% of outpatient pulmonary practice Cost > $1 billion/yr. (excludes diag. tests & meds) Cough complications Intrathoracic pressures 300 mmHg; exp velocity 500 mph Exhaustion, insomnia, headache, musculoskel pain, dizziness, urinary incontinence, xs persperation --ACCP: Consensus Statement on Cough. Chest 2006

Spectrum of Reasons Patients Seek Medical Care for Cough Reassurance nothing serious (77%) Concern that something serious is wrong (72%) Frequent retching (56%) Exhaustion (54%) Others think something wrong (53%) Embarrassment/self-consciousness (47%) Difficulty speaking on the phone (39%) Hoarseness (39%) --ACCP: Consensus Statement on Cough. Chest 2006

Cough Reflex Each cough occurs through the stimulation of a complex reflex arc. This is initiated by the irritation of cough receptors that exist not only in the epithelium of the upper and lower respiratory tracts, but also in the pericardium, esophagus, diaphragm, and stomach. Chemical receptors sensitive to acid, heat, and capsaicin-like compounds trigger the cough reflex via activation of the type 1 vanilloid (capsaicin) receptor [3-5]. In addition, mechanical cough receptors can be stimulated by triggers such as touch or displacement. Laryngeal and tracheobronchial receptors respond to both mechanical and chemical stimuli. Impulses from stimulated cough receptors traverse afferent nerves (vagus, glossopharyngeal, trigeminal, or phrenic) to a "cough center" in the medulla, which itself may be under some control by higher cortical centers. Sex-related differences in cough reflex sensitivity explain the observation that women are more likely than men to develop chronic cough [1,6-8]. The cough center generates an efferent signal that travels down the vagus, phrenic, and spinal motor nerves to expiratory musculature to produce the cough. 3. Morice, AH, Geppetti, P. Cough. 5: The type 1 vanilloid receptor: a sensory receptor for cough. Thorax 2004; 59:257. 4. Trevisani, M, Milan, A, Gatti, R, et al. Antitussive activity of iodo-resiniferatoxin in guinea pigs. Thorax 2004; 59:769. 5. Groneberg, DA, Niimi, A, Dinh, QT, et al. Increased expression of transient receptor potential vanilloid-1 in airway nerves of chronic cough. Am J Respir Crit Care Med 2004; 170:1276. 6. Morice, A, Kastelik, JA, Thompson, RH. Gender differences in airway behaviour. Thorax 2000; 55:629. 7. Kastelik, JA, Thompson, RH, Aziz, I, et al. Sex-related differences in cough reflex sensitivity in patients with chronic cough. Am J Respir Crit Care Med 2002; 166:961. 8. Morice, AH, Kastelik, JA. Cough * 1: Chronic cough in adults. Thorax 2003; 58:901. *Chemical Receptors (type 1 vanilloid): acid, heat, capsaicin-like compounds Mechanical Receptors: Touch/displacement Note: sex-related difference in sensitivity…women more likely to develop chronic cough UTD 2009

What are the most common causes of chronic cough? …after excluding smoker’s cough & ACE inhibiter

Common Causes of Chronic Cough Upper Airway Cough Syndrome (38-87%) (formerly post nasal drip syndrome) Asthma (14-43%) GERD (10-40%) Chronic Bronchitis (0-12%) More than one cause (24-72%) --Irwin et al: Chest 1998;114:133S; Irwin et al: ARRD 1990; 141:640; Irwin et al: ARRD 1981; 123:413; Pratter et al: Ann Int Med 1993; 119:977

Upper Airway Cough Syndrome (UACS) Formerly Post Nasal Drip 3/4 studies: UACS most common cause chronic cough DDx: Allergic, perennial (non)allergic, vasomotor rhinitis, nasopharyngitis, sinusitis, rhinitis medicamentosa, pregnancy, abnl nasal/sinus anatomy Symptoms: nasal discharge, post nasal drip, frequent throat clearing May not be apparent to the patient Exam: cobblestone/secretions in nasopharynx Response to Rx usually secures diagnosis Try empiric Rx for UACS before extensive w/up for cause of cough

Asthma History includes episodic wheezing and dyspnea “Cough variant asthma”…no wheezing/dyspnea, only cough, normal spirometry Other clues from history: atopy, family history of asthma, seasonal, follows URI, worsens with exposure to cold/dry air, fragrances or fumes, exacerbated by -blocker Rx Bronhoprovocation tests: Good negative predictive value; + test c/w but not diagnostic (false + ~ 33%) Diagnosis: improvement post therapeutic trial (e.g., -agonist x 1 week)

Eosinophilic Bronchitis or Non-Asthmatic EB Distinct from asthma; no bronchospasm Recognized 2002; frequency uncertain (European studies 10-15%), probably under diagnosed Clinical characteristics Unexplained nonproductive cough Atopic; normal spirometry & bronchoprovocation tests (Induced) Sputum eosinophilia & airway inflammation Bronchial biopsy is diagnostic: Eosinophilic inflammation, but no Mast cells (or BAL w/ lots of Eosinophils) Treatment: Inhaled steroid Natural history not certain (N=367; 1 yr f/u): 55% persistent symptoms; 33% asymptomatic 12% develop asthma… Gibson et al: Thorax 2002 Rytila et al: Eur Respir J 2000

Gastroesophageal Reflux (GERD) Second most common cause of cough in elderly Up to 40% cases (Mello et al: Arch Int Med 1996; 156:997) Experimental data: Acid in distal esoph. can mimic cough, blunted by lidocaine or inhaled ipatropium, does not elicit cough in normals Laryngeal-Pharyngeal Reflux (LPR): consider Oto eval (Clues: throat clearing, hoarseness, globus sensation, VCD) Empiric 2 week trial with proton pump inhibitor =/more reliable than pH monitor (Ours et al: Am J. Gastroent 1999) NB: May take >8 wks of PPI Rx Acid suppression may not Rx reflux GERD can contribute to asthma exacerbation

Chronic Bronchitis “Smoker’s Cough” Definition Most are smokers, but most smokers don’t seek attention for “smoker’s cough” Sputum clear/white Change in character purulent sputum: infection (viral, bacterial) ? Neoplasm

Common Causes of Chronic Cough Upper Airway Cough Syndrome (38-87%) Asthma (14-43%) GERD (10-40%) Chronic Bronchitis (0-12%) More than one cause (24-72%) Hickam’s Dictum vs. Occum’s Razor A patient may have as many diagnoses as he darn well pleases! --Irwin et al: Chest 1998;114:133S; Irwin et al: ARRD 1990; 141:640; Irwin et al: ARRD 1981; 123:413; Pratter et al: Ann Int Med 1993; 119:977

Can you name some of the uncommon causes of chronic cough?

Less Common Causes of Chronic Cough Bronchiectasis (0-5%) ACE inhibitor Rx Post-infectious Occult aspiration Lung Cancer Obstructive Sleep Apnea Occult CHF Interstitial Pulmonary Fibrosis Occult infection (eg, TB, NTM, suppurative bronchitis) Foreign body Broncholith Eosinophilic Bronchitis Industrial bronchitis Nasal polyps Problems with: Auditory canal Larynx Diaphragm Pleura Pericardium Esophagus Psychogenic --Irwin et al: Chest 1998;114:133S; Irwin et al: ARRD 1990; 141:640; Irwin et al: ARRD 1981; 123:413; Pratter et al: Ann Int Med 1993; 119:977

Cough & Sleep Cough suppression during REM & non-REM sleep occurs naturally “Cough Variant Obstructive Sleep Apnea”… 44% chronic cough pts have OSA Hx not suggestive of OSA, cough only manifestation Risk Factors: Female, nocturnal heartburn, rhinitis Not associated: BMI, Epworth Sleepiness Scale, Dyspnea, snoring CPAP treatment relieves cough Chan KK et al. Eur Resp J 2010;35:368-72 Sundar KM et al. Cough 2010;6:2-8

Bronchiectasis Repeated/persistent airway inflammation & damage poor mucous clearance; secretion pooling dilated bronchi; thickened bronchial wall chronic infection Cough with mucopurulent sputum Chest x-ray insensitive, but may show crowded lung markings, thickened bronchial walls, fluid-filled cystic bronchi, “tram-tracks”, “signet ring” High resolution chest CT more specific

Engagement (Signet) ring: Thin Section CT (1.5-3 mm) Normal: Engagement (Signet) ring: Other Characteristics Lack of tapering of bronchi Clusters = Grape-like appearance Enlarged bronchi can appear cystic vs. Bullae of emphysema (thinner walls) Distribution of bronchiectasis suggests Dx CentralABPA; Upper lobe  CF; Lobar  Post-infectious; obstructive (eg, LN, FB) Bronchus Vessel Bronchus Vessel

Bronchiectasis Differential Diagnosis Post-infectious (e.g. Pertussis, severe pneumonia, Mycobacterium tuberculosis or avium complex) Airway obstruction or recurrent aspiration Cystic Fibrosis (Case report: Dx made at 65) Immunodeficiency (Agammaglobulinemia) Esoterica… Alpha-1-Antitrypsin Deficiency Inflammatory Disease (eg, Sjogren’s) Allergic Bronchopulmonary Aspergillosis Dyskinetic Cilia Syndrome Diffuse Pan Bronchiolitis Young’s Syndrome

Mnemonic: IA-SPICE Idiopathic Airway Obstruction Sjogren’s & other inflammatory (RA, IBD) Post-Infectious (Pertussis, Pneumonia, MAC, Mtb) Immunodeficiency (Agammaglobulinemia Cystic Fibrosis Esoterica Alpha-1-Antitrypsin Deficiency Dyskinetic Cilia Syndrome Allergic Bronchopulmonary Aspergillosis Diffuse Pan Bronchiolitis Young’s Syndrome

Pulmonary Fascinoma with an Infectious Attitude 77 yo WF, persistent non-productive cough x 4.5 yrs Nonsmoker, denies S/S of PND, GERD, Asthma H/O ovarian cancer resection 4.5 years ago Right middle lobe infiltrate on CXR Bronchoscopy by local surgeon: Mycobacterium avium complex Advice: nonpathogen, no treatment Cough worsening severity over the last 1 year Intermittent night sweats, temp 99 More fatigue, increased dyspnea, no weight loss CXR & CT

WF. 77 y.o. F

What is your working diagnosis? What would you do now? Case Summary (cont’d) CXR varies little, going back 4.5 years 1 year ago (another university MD) bronchoscopy: Biopsy: non-caseating granulomas; AFB Lavage: Mycobacterium avium complex (MAC) Advice: nonpathogen, no specific treatment Failed therapeutic trials: bronchodilators, steroids (oral/inhaled), & H2 blockers What is your working diagnosis? What would you do now?

Page 3, The Rest of the Story Page 3, The Rest of the Story... Nodular Bronchiectais (Lady Windemere’s Syndrome) AM Sputa x 3 smear positive AFB; grew MAC Treated for MAC Sputa cleared; cough/fatigue/night sweats resolved by 6 mos. Non-productive cough returned at 9 months; AM sputa remained negative for MAC W/u revealed GERD; possibly allergic rhinitis Resolved with proton pump inhibitor & nasal steroid

MAC Lung Infections Majority of NTM respiratory isolates are MAC and are pathogenic in 50% cases Incidence rising…~8/100,000 Worldwide, most common in temperate regions Isolated in bedding mat’l, house dust, soil, plants, swimming pools, hospital H2O, natural bodies of H2O Most infections: rural locations in SE, Atlantic & Pacific coastal regions of US Reactivity with PPD-B (70%) highest in southeast

MAC Skin Test Reactors Distribution Edwards et al: ARRD 1969

MAC Lung Infection— Nodular/Bronchiectasis Form Persistent cough, dyspnea, malaise, weakness Symptoms antedate MAC diagnosis (months-years) Elderly>>young, Non-smoking female >>male w/o pre-existing lung disease Pathogenesis uncertain Medically uninitiated women; Lady Windermere’s syndrome implies pathogenesis linked to fastidiousness, habitual cough suppression Body morphotype: Tall/thin plus increased a/w Pectus excavatum, Scoliosis, Mitral valve prolapse, Joint hypermobility Undetectable defect in muco-cilliary fxn or mucosal immunity Linked to gene for multi-drug intolerance Chronic indolent process (symptoms can spontaneously abate) MAC Infection is not the disease, but symptom of the disease Patients die with, rather than from disease (Mortality estimates: 5-20%) Oscar Wilde’s play 1892…Lady Windemere’s fan

Anthropometrics of women w/ N/B NTM Disease Data from NIH study on Anthropometrics… Left panel shows schematic depiction of the anthropometrics of the women with pulmonary nontuberculous mycobacterial (PNTM) (n = 60) compared with (right panel) National Health and Nutrition Examination Survey age-, sex-, and race-matched control subjects. *P < 0.001. …Marfan’s question: Because Marfan syndrome is also associated with leanness, increased height, scoliosis, and mitral valve prolapse, we examined body segment ratios and other physical findings that are highly correlated with Marfan syndrome. The frequency of high-arched palate in PNTM was 79%, which is similar to the reported rate of 60–75% in Marfan syndrome (30). However, none of our 63 patients met major criteria for skeletal involvement under the revised (Ghent) diagnostic criteria for Marfan syndrome (31). The mean upper:lower body segment ratio in PNTM infection was 0.99 (vs. <0.86 in Marfan), and the mean armspan:height ratio was 1.00 (vs. >1.05 in Marfan). Only 38% had positive wrist and thumb signs, and only 24% had the benign joint hypermobility syndrome, compared with 85% of patients with Marfan syndrome (32). Therefore, this is a morphologic syndrome distinct from Marfan syndrome. Kim et al AJRCCM 2008; 178:1066

MAC Lung Infection— Nodular/Bronchiectasis Form Persistent cough, dyspnea, malaise, weakness Symptoms antedate MAC diagnosis (months-years) Elderly>>young, Non-smoking female >>male w/o pre-existing lung disease Pathogenesis uncertain Medically uninitiated women; Lady Windermere’s syndrome implies pathogenesis linked to fastidiousness, habitual cough suppression Body morphotype: Tall/thin plus increased a/w Pectus excavatum, Scoliosis, Mitral valve prolapse, Joint hypermobility Undetectable defect in muco-cilliary fxn or mucosal immunity Linked to gene for multi-drug intolerance Chronic indolent process (symptoms can spontaneously abate) MAC Infection is not the disease, but symptom of the disease Patients die with, rather than from disease (Mortality estimates: 5-20%) Oscar Wilde’s play 1892…Lady Windemere’s fan

MAC Lung Infection-- Nodular/Bronchiectasis Form (cont’d) Episodic co-infection by other organisms (P. aeruginosa, Nocardia, rapidly growing mycobacteria) Chest x-ray: (non-cavitary) infiltrates in middle lobe or lingula…Inadequate to appreciate N/B pattern High resolution chest CT: Bronchiectasis (multi-lobe more common) Large and small (<5 mm) nodules (centrilobular) Peripheral “tree-in-bud” pattern

Location of Infiltrates Kennedy & Weber: AJRCCM 1994

MAC Lung Infection-- Nodular/Bronchiectasis (cont’d) Episodic co-infection by other organisms (P. aeruginosa, Nocardia, rapidly growing mycobacteria) Chest x-ray: (non-cavitary) infiltrates in middle lobe or lingula…Inadequate to appreciate N/B pattern High resolution chest CT: bronchiectasis (multi-lobe) Large and small (<5 mm) nodules (centrilobular) Peripheral “tree-in-bud” pattern

General MAC Lung Infection Treatment Careful patient selection ~50% nonpathogen ATS/IDSA criteria Expensive, long duration, intolerance & toxicity (elderly), compliance Extended spectrum macrolides Clarithro- > azithromycin Improved outcomes to ~80% clinical cure (40%) >90% susceptibility if previously untreated Continue treatment until culture neg. x 12 months

MAC Lung Infection Treatment (cont’d) Nodular/Bronchiectasis: Clarithro- 1 gm TIW or Azithro- 500 mg TIW Ethambutol 25 mg/kg TIW Rifampin 600 mg TIW Adjunctive measures: nutrition, chest physiotherapy, surgery Susceptibility testing unreliable except Clarithro- Severe disease: Strep or Amikacin; Rifabutin vs Rifampin

Nodular Bronchiectasis/MAC (Lady Windemere’s) Take Home Points Mycobacteria avium complex is an unusual cause of cough in the general clinic MAC as a pathogen in the “normal host” is frequently not appreciated…Recall Morphotype CT will show nodular bronchiectasis, tree-in-bud, inflammatory nodules Symptoms for years before diagnosis common Specific antibiotic treatment successful in some but not all cases (medication intolerance common) Some patients may exhibit several causes for cough that require treatment simultaneously. …Hickam’s Dictum!

Post-Infectious Cough Diagnosis of exclusion Cough post viral or other URI can persist for 8 weeks Mycoplasma, Chlamydia, B. pertussis Proposed mechanisms: Post nasal discharge Enhanced sensitivity of airway (exposure of cough afferent nerves in epithelia due to epithelial necrosis) Airway hyper-responsiveness

Return of the 100 day Cough… No. & Incidence of Pertussis Cases Among Adults (19-64yo) 2000-2004 CDC: MMWR Rec&Rep Dec 15, 2006

Post-infectious Cough: Pertussis in Adults B. pertussis (GNB)…very contagious Household: 70-100% of contacts School: 50-80% of contacts Increased incidence (highest among 10-19 yo) Immunization effect wanes during 1st 10 yrs post vaccination Decreasing # adults carrying natural immunity obtained during pre-vaccine era Clinical characteristics Incubation period: 1-3 wks Viral-like initial phase (catarrhal): ~2 weeks (conjunctivitis, rhinorrhea, fever, cough late) Paroxysmal phase: 3-6 months, Worsening cough (whoop uncommon…post-tussive vomiting) Note: Protracted cough may be the only symptom, & Many infection can result in no cough (elderly)

Pertussis in Adults II Diagnosis Treatment Catarrhal Phase NP aspirate or polymer swab of NP for culture PCR costly supplement dx (CDC rec w/ culture) Acute & convalescent IgG or IgA titers (PT or FHA) Cough & linkage w/ confirmed case Treatment Catarrhal Phase Macrolide (erythro-, azithro-, clarithromycin) Don’t delay Rx waiting for confirmation tests Isolation for 5 days from start or Rx Treatment Paroxysmal Phase: See Post-infectious cough recommendations Prevention after exposure Macrolide Rx same as Treatment dose/duration Vaccination w/ acellular pertussis vaccine (Tdap)

Pertussis in Adults: Vaccination Issues ACIP Recommendations Tdap: Tetanus, Diphtheria, Acellular Pertussis Booster Tdap in adolescents, 11-18 yr Single Tdap booster for Adults 19-65 yr recommended Improve adult coverage for pertussis, but also tetanus & diphtheria. Single dose replacing Td at q10 year booster <10 yr interval Td (as short as 2 years) HCW high risk for exposure (Cost benefit for vaccination program over outbreak control cost) Health care personnel (HCP) are at risk for being exposed to pertussis in both inpatient (acute and longterm care) and outpatient facilities. Infected personnel can then expose at-risk neonates, children and adults. Numerous nosocomial outbreaks of pertussis have been attributed to HCP exposure and infection, with considerable morbidity and mortality [46]. Investigation and control measures to prevent pertussis after unprotected exposure in such settings are labor intensive and costly. Tdap vaccination in adult healthcare workers has been shown to be effective in controlling nosocomial outbreaks of pertussis [46,62]. A cost-benefit analysis found that the cost of vaccinating healthcare workers is considerably less than the costs associated with a hospital outbreak [63]. It is estimated that the introduction of a hospital employee vaccination program would result in a median net savings of $95,000; for every dollar spent on the vaccination program, the hospital would save $2.38 on control measures [46]. The ACIP and the Healthcare Infection Control Practices Advisory Committee (HICPAC) recommend that unvaccinated HCPs who have direct patient contact should receive a single Tdap vaccination as soon as feasible; an interval of >two years from the last Td is advised, but the vaccine may be given at shorter intervals. (See "Immunizations for healthcare workers".) New personnel should be asked if they have recently been vaccinated with Td or Tdap, and vaccinated with Tdap, if appropriate, when they begin employment. Catch-up vaccination should be encouraged for existing personnel. One strategy is to incorporate Tdap vaccination with an annual influenza vaccine campaign, or to use tactics similar to influenza vaccination campaigns if not done together. Some health care facilities might find it necessary to vaccinate using a two-tiered strategy, initially prioritizing HCPs with contact with infants, immunocompromised patients, or other high risk patient groups. HCPs without direct patient contact should receive a single dose of Tdap to replace their next scheduled Td vaccine. CDC: MMWR Rec&Rep Dec 15, 2006 ACIP 2009

ACE Inhibitor 3-20% of patients on ACE Inhibitor Rx 72% recur, if re-administered Accumulation of bradykinin (normally degraded by ACE) Note: Angiotensin II receptor antagonists (e.g. losartan) do not cause cough General features: Starts ~1 wk after start of Rx (delayed up to 6 months) Resolves 1-4 d after stopping Rx (can take up to 4 weeks) Recurs with same or different ACE inhib Women > men Incidence no greater in asthmatics No change in spirometry Rx = Stop ACE inhib. (Angiotensin II receptor blocker)

General Approach UACS, Asthma, and GERD cause 90% chronic cough If nonsmoker, not on ACE inhibitor, normal or stable CXR, then 99% cases due to above 3 causes Pratter et al: Antihistamine-decongestant Rx was only Rx needed in 36% & another 50% noted improvement in symptoms. Guidelines Recall Hickam’s Dictum! Hx, Px, CXR, Rx aimed at clues in evaluation If no clues, start antihistamine-decongestant or nasal steroid If no improvement, check spirometry/bronchoprovocation; add bronchodilators If no improvement, 24hr esoph pH monitoring

Specific Treatments Upper Airway Cough Syndrome (UACS) Anti-histamine/decongestant 1st generation sedating anti-histamines more effective Effect takes ~1 week Nasal steroids May take up to 2 weeks for full effect Add nasal ipratropium if anti-histamine or decong. failing (Vasomotor rhinitis) Trial monteleukast if allergic rhinitis & above insufficient Sinusitis Document with limited sinus CT Anti-histamine/decong. + abx (bactrim, cefurox) up to 6 wks Short term nasal decongestant spray

Antihistamine and Driving Performance Randomized, double-blinded, double dummy, N=40 (ages 25-40) Compared fexofenadine, diphenhydramine, EtOH (0.1%), & placebo, 4 period x-over trial Results (Driving Simulator): Driving performance was poorest with diphenhydramine (vs. EtOH or fexofenadine) Drowsiness self-assessment scores did not predict worse driving performance Drivers perception of drowsiness on diphenhydramine (50 mg) not a good indicator of when they should not drive Weiler et al: AIM 2000

Specific Treatments Upper Airway Cough Syndrome (UACS) Anti-histamine/decongestant 1st generation sedating anti-histamines more effective Effect takes ~1 week Nasal steroids (and/or nasal antihistamine) May take up to 2 weeks for full effect Add nasal ipratropium if anti-histamine or decong. failing (Vasomotor rhinitis) Trial Monteleukast if allergic rhinitis & above insufficient Sinusitis Document with limited sinus CT Anti-histamine/decong. + abx (bactrim, cefurox) up to 6 wks Short term nasal decongestant spray

Specific Treatments Cough Variant Asthma Same principles as asthma Inhaled bronchodilator trial; consider 1-2 week course of Prednisone (diagnostic & therapeutic) Most require maintenance inhaled steroid Limited data for leukotriene receptor antagonists 2 weeks prednisone usually sufficient --Cheriyan et al: Ann All 1994

Specific Treatments GERD Avoidance of reflux-inducing food (e.g., fatty foods, chocolate, EtOH) Smoking cessation Avoid snacking No eating within 3 hrs of lying down for sleep Elevation of head of bed H2 antagonist or Proton pump inhibitor (preferred) Length of time for response may be 3-6 mos. Refractory cases: LPR requires high dose PPI May be d/t dyskinesis (trial metocolpromide) Rare pt, acid suppressed still cough d/t reflux  surgery --Irwin et al: ARRD 1990 & Irwin et al: Chest 1993

Non-specific Treatments Post-infectious: nasal steroid or ipratropium MDI (steroid B/T) Ipratropium MDI Blocks afferent limb of cough reflex Alters mucociliary factors  less stimulation of cough receptors Central acting anti-tussive agents Codeine 30 mg Dextramethoraphan, up to 60 mg Meta analysis (Yancy et al. Chest 2013;144:1827-38) both > placebo; no good comparison studies, no studies examine chronic/refractory cough Peripherally acting agents Benzonatate: inhibits stretch receptors (Rx x50yrs) Guaifenesin: hydrates mucous for expectoration; may suppress hypersensitive cough receptors Studied but not generally useful when used empirically Inhaled steroids Inhaled lidocaine Refractory Cough or no definable cause can be as common as 40% Referred to as Cough Hypersensitivity Syndrome…Three possible causes (From Godsobel J All Clin Imm Sept 2012) Post Viral neuropathy (sensory neuropathy and requires gabapentin, pregabalin, or amitriptyline) Laryngeal dysfunction w/ chronic cough and throat clearing…oft sense dyspnea and VCD is a factor. Respond to speech Rx Irritable larynx syndrome. Methacholine induces cough or VCD and Rx aimed at decreasing irritation

Summary Differentiate acute from chronic cough Reviewed the most common causes as well as uncommon causes of chronic cough Identified treatment strategies