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

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Title: Common%20and%20Uncommon%20Causes%20of%20Chronic%20Cough


1
Common and Uncommon Causes of Chronic Cough
  • Douglas B. Hornick, MD
  • Professor
  • Division of Pulmonary, Critical Care, and
    Occupational Medicine
  • University of Iowa

2
Objectives
  • Differentiate acute from chronic cough
  • Review the most common causes as well as
    uncommon causes of chronic cough
  • Discuss treatment strategies

3
Great Reference
Irwin RS, et al Diagnosis Management of
Cough ACCP Evidence-based Clinical Practice
Guidelines. Chest 2006 1291S-292S.
4
How do you define chronic cough?
5
Definitions Epidemiology
  • Cough persisting gt 3 weeks
  • Acute up to 3 weeks
  • Subacute 3-8 weeks
  • Chronic gt8 weeks
  • 2008 Most common symptom among outpatients
    (gt26 million office visits US)
  • 40 of outpatient pulmonary practice
  • Cost gt 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
6
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
7
Cough Reflex
Chemical Receptors (type 1 vanilloid) acid,
heat, capsaicin-like compounds Mechanical
Receptors Touch/displacement Note sex-related
difference in sensitivitywomen more likely to
develop chronic cough
UTD 2009
8
What are the most common causes of chronic cough?
after excluding smokers cough ACE inhibiter
9
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 1998114133S Irwin et al
ARRD 1990 141640 Irwin et al ARRD 1981
123413 Pratter et al Ann Int Med 1993 119977
10
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

11
Asthma
  • History includes episodic wheezing and dyspnea
  • Cough variant asthmano 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)

12
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 (N367 1 yr f/u)
  • 55 persistent symptoms 33 asymptomatic
  • 12 develop asthma

Gibson et al Thorax 2002 Rytila et al Eur
Respir J 2000
13
Gastroesophageal Reflux (GERD)
  • Second most common cause of cough in elderly
  • Up to 40 cases (Mello et al Arch Int Med 1996
    156997)
  • 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 gt8 wks of PPI Rx Acid
    suppression may not Rx reflux GERD can
    contribute to asthma exacerbation

14
Chronic Bronchitis Smokers Cough
  • Definition
  • Most are smokers, but most smokers dont seek
    attention for smokers cough
  • Sputum clear/white
  • Change in character
  • purulent sputum infection (viral, bacterial)
  • ? Neoplasm

15
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)

Hickams Dictum vs. Occums Razor A patient may
have as many diagnoses as he darn well pleases!
--Irwin et al Chest 1998114133S Irwin et al
ARRD 1990 141640 Irwin et al ARRD 1981
123413 Pratter et al Ann Int Med 1993 119977
16
Can you name some of the uncommon causes of
chronic cough?
17
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 1998114133S Irwin et al
ARRD 1990 141640 Irwin et al ARRD 1981
123413 Pratter et al Ann Int Med 1993 119977
18
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 201035368-72 Sundar
KM et al. Cough 201062-8
19
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

20
  • 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
21
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, Sjogrens)
  • Allergic Bronchopulmonary Aspergillosis
  • Dyskinetic Cilia Syndrome
  • Diffuse Pan Bronchiolitis
  • Youngs Syndrome

22
Mnemonic IA-SPICE
  • Idiopathic
  • Airway Obstruction
  • Sjogrens 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
  • Youngs Syndrome

23
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

24
WF. 77 y.o. F
25
Case Summary (contd)
  • 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?
26
Page 3, The Rest of the Story... Nodular
Bronchiectais (Lady Windemeres 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

27
MAC Lung Infections
  • Majority of NTM respiratory isolates are MAC and
    are pathogenic in 50 cases
  • Incidence rising8/100,000
  • Worldwide, most common in temperate regions
  • Isolated in bedding matl, 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

28
MAC Skin Test Reactors Distribution
Edwards et al ARRD 1969
29
MAC Lung Infection Nodular/Bronchiectasis Form
  • Persistent cough, dyspnea, malaise, weakness
  • Symptoms antedate MAC diagnosis (months-years)
  • Elderlygtgtyoung, Non-smoking female gtgtmale w/o
    pre-existing lung disease
  • Pathogenesis uncertain
  • Medically uninitiated women Lady Windermeres
    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)

30
Anthropometrics of women w/ N/B NTM Disease
Kim et al AJRCCM 2008 1781066
31
MAC Lung Infection Nodular/Bronchiectasis Form
  • Persistent cough, dyspnea, malaise, weakness
  • Symptoms antedate MAC diagnosis (months-years)
  • Elderlygtgtyoung, Non-smoking female gtgtmale w/o
    pre-existing lung disease
  • Pathogenesis uncertain
  • Medically uninitiated women Lady Windermeres
    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)

32
MAC Lung Infection-- Nodular/Bronchiectasis Form
(contd)
  • Episodic co-infection by other organisms (P.
    aeruginosa, Nocardia, rapidly growing
    mycobacteria)
  • Chest x-ray (non-cavitary) infiltrates in middle
    lobe or lingulaInadequate to appreciate N/B
    pattern
  • High resolution chest CT
  • Bronchiectasis (multi-lobe more common)
  • Large and small (lt5 mm) nodules (centrilobular)
  • Peripheral tree-in-bud pattern

33
Location of Infiltrates
Kennedy Weber AJRCCM 1994
34
MAC Lung Infection-- Nodular/Bronchiectasis
(contd)
  • Episodic co-infection by other organisms (P.
    aeruginosa, Nocardia, rapidly growing
    mycobacteria)
  • Chest x-ray (non-cavitary) infiltrates in middle
    lobe or lingulaInadequate to appreciate N/B
    pattern
  • High resolution chest CT
  • bronchiectasis (multi-lobe)
  • Large and small (lt5 mm) nodules (centrilobular)
  • Peripheral tree-in-bud pattern

35
General MAC Lung Infection Treatment
  • Careful patient selection
  • 50 nonpathogen
  • ATS/IDSA criteria
  • Expensive, long duration, intolerance toxicity
    (elderly), compliance
  • Extended spectrum macrolides
  • Clarithro- gt azithromycin
  • Improved outcomes to 80 clinical cure (40)
  • gt90 susceptibility if previously untreated
  • Continue treatment until culture neg. x 12 months

36
MAC Lung Infection Treatment (contd)
  • 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

37
Nodular Bronchiectasis/MAC (Lady
Windemeres) 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 appreciatedRecall 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.

Hickams Dictum!
38
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

39
Return of the 100 day Cough
CDC MMWR RecRep Dec 15, 2006
40
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 uncommonpost-tussive vomiting)
  • Note Protracted cough may be the only symptom,
    Many infection can result in no cough
    (elderly)

41
Pertussis in Adults II
  • Diagnosis
  • 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)
  • Dont 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)

42
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
  • lt10 yr interval Td (as short as 2 years)
  • HCW high risk for exposure (Cost benefit for
    vaccination program over outbreak control cost)

CDC MMWR RecRep Dec 15, 2006 ACIP 2009
43
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 gt men
  • Incidence no greater in asthmatics
  • No change in spirometry
  • Rx Stop ACE inhib. (?Angiotensin II receptor
    blocker)

44
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 Hickams Dictum!
  • Hx, Px, CXR, Rx aimed at clues in evaluation
  • If no clues, start antihistamine-decongestant or
    nasal steroid
  • If no improvement, check spirometry/bronchoprovoca
    tion add bronchodilators
  • If no improvement, 24hr esoph pH monitoring

45
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

46
Antihistamine and Driving Performance
  • Randomized, double-blinded, double dummy, N40
    (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
47
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

48
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

--Cheriyan et al Ann All 1994
49
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
50
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
    20131441827-38) both gt 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

51
Summary
  • Differentiate acute from chronic cough
  • Reviewed the most common causes as well as
    uncommon causes of chronic cough
  • Identified treatment strategies
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