2COUGHOne of the most common symptoms for which patients seek medical attentionDefensive reflex that enhance the clearance of secretions and particles from the airwayProtects the lower airways from the aspiration of foreign materials
3Coughing may be initiated either voluntarily or reflexively. It has both afferent and efferent pathways .The cough starts with a deep inspiration followed by glottic closure, relaxation of the diaphragm, and muscle contraction against a closed glottis.
4Classification Acute cough Subacute cough Chronic Cough ~ 3 to 8 weeks ~ maximum of 3 weeksSubacute cough~ 3 to 8 weeksChronic Cough~ more than 8 weeksClassification of cough based on symptom duration issomewhat arbitraryAcute cough (<3 weeks)Is most often due to upper respiratory infection (common cold, acute bacterial sinusitis, and pertussis), serious disorders, such as pneumonia, pulmonary embolus, and congestive heart failure, can also present in this fashion.Sub acute cough (between 3 and 8 weeks)Is commonly post-infectious, resulting from persistent airway inflammation and/or postnasal drip following viral infection, pertussis, or infection with Mycoplasma or Chlamydia.Chronic cough (>8 weeks)In a smoker raises the possibilities of asthma, COPD or bronchogenic carcinoma, Eosinophilic Bronchitis , Esophageal Disease, Post Nasal Drip , ACEI , Smoking.De Blasio et al. Cough 2011, 7:7
5ETIOLOGYAcute cough~ maximum of 3 weeksUpper Respiratory Infection (common cold, acute bacterial sinusitis, and pertussis)PneumoniaPulmonary embolusCongestive cardiac failureSubacute cough~ 3 to 8 weeksPost-infectiousPostnasal drip following viral infection,PertussisTuberculosisMycoplasma or Chlamydia infectionChronic Cough~ more than 8 weeksAsthmaCOPDBronchogenic carcinomaEosinophilic BronchitisEsophageal Disease,Post Nasal DripACEISmoking.
6 Chronic Cough- Etiology In non-smoking adults with a normal CXR who are not taking ACE inhibitors, chronic cough is almost always due to which of the following 3 conditions?Congestive Heart FailureUpper Airway Cough Syndrome (UACS)c) Asthmad) Gastroesophageal reflux disease (GERD)e) Chronic Bronchitis
10Guideline for Evaluating Chronic Cough • A systematic, diagnostic approach has been validated in immunocompetent patients- 5 steps plan: Step 1: Review history and exam focusing on the most common causes of chronic cough
11History taking History Reasons Onset To determine acute/subacute or chronic causes of coughAggravating factor, relieving factorCough due to GERD affected by postural changes, post mealCold induced or MDI relieved cough in asthma or COPDSputum colourNormal sputum: clear to white colour, thin, odourless n tastelessYellow-green: bacterial infectionRust-colored: pneumoniaSputum characterMucoid or mucopurulent: cigarette smokers as a result of chronic bronchitisCommonly purulent in bronchiestasisSputum amountSignificant volumes: more than 1 cup per day
12Wheezing suggest asthma/COPD HistoryReasonsFeverOngoing infectionSOBRespiratory distressNoisy breathingWheezing suggest asthma/COPDLoss of appetite, loss of weight, hemoptysisSuggesting Tuberculosis, malignancyAllergy, nasal obstruction or congestion, rhinorrhoea, sneezing, facial pain, post-nasal drip or repetitive throat clearanceSuggesting RhinosinusitisDyspepsia, heartburn, waterbrashGERDMedication usedACE-inhibitorOccupationExposure to asbestos, chemical or cigarette smokeFamily historyAsthma, tuberculosis, lung cancer, cystic fibrosisSocial historyContact with PTB suggesting PTBReflux: usually caused by transient relaxation of low esophageal sphincter. Thus, relaxation cough may occur after meal, during meal, supine, bending orstooping position: diminish at sleep (LOS closed) but recur on adopting an upright position: talking, laughing may precipitate reflux cough (diaphragm important component of LOS)Dyspnoea, wheezing n chest tightness suggest asthma but can be absent in CVA-variability from day to day and nocturnal exacerbation suggestivePharyngeal sm: rhinosinusitis: many of these sm also occur in reflux disease. GERD may be suggested by presence of classic sm – dyspepsia, heartburn, water brashACE-I :< 15% patient on ACE-I develop dry cough soon after commencement: usially disappear after cessation of tx but resolution may takes several months, may persists in small minority.
13Physical Examination Physical examination Reasons General condition such as altered conscious level, accessory muscles usage, cyanosis, grunting, nasal flaring, clubbing, nicotine stainTo assess severity and to look for respiratory distressVital signsFever – infectionTachycardia, tachypnoea – respiratory distressPulsus paradoxus – asthmaNasal polypsAllergy rhinitisPharynx: erythema, a cobblestone appearance of posterior pharyngeal mucosa or mucoid secretions dripping from the nasopharynxPost nasal dripChest:HyperinflatedRecessionSilent chestCrepitations, wheezingSuggest air trapping due to chronic diseaseRespiratory distressSevere asthmaPneumonia, asthma, heart failure
14Physical examinationReasonsCVS: Displaced apex beat, raised JVP, loud P2, RV heaveCor pumonaleEczema, transverse nasal crease, injected conjunctivaSigns of atopic diseaseLymphadenopathyTo suggest infectionAbnormal physical signs are rare in a chronic dry coughWheeze may be audible on examination but is usually absent in cough variant asthma (CVA)
15Guideline for Evaluating Chronic Cough Step 2: Order a CXR in all patientsStep 3: Do not order additional tests in present smokers or patients taking ACE inhibitors until the response to smoking cessation or drug discontinuation for at least 4 weeks can be assessed.- Cough due to smoking or ACE inhibitors shouldimprove substantially or disappear during thistime- frame of abstinence.Step 4: Order additional diagnostic tests or embark on empiric treatment
16Investigations Spirometry: -demonstrate significant airway reversibility (asthma)-unavailable or normal and history suggestive: serialmeasurement of PEF (diurnal variability)Bronchoprovocation test :- negative: rules out asthma but does not rules outsteroid- responsive coughPlain sinus radiography: low specificity but improves with history and findingsSputum eosinophiliaCxr mandatory a early stage as is significant abnormality will alter the diagnostic algorithm and avoid unnecessary Ix.Spirometry : before and after inhaled bronchodilatorBronchoscopy: Suspected FB, CXR showing mass, pulmonary, lobar or segmental collapse, hemoptysis, recurrent pneumonia in the same areaFibreoptic bronchoscopy – biopsyHigh Resolution CT scan: lung parenchymal disease or bronchiectasis (not appreciated from hx and CXR)
20Guideline for Evaluating Chronic Cough Step 5: Determine the cause(s) of cough by observing which specific therapy eliminates cough • If the evaluation suggests more than one possible cause, initiate treatment in the same sequence that the abnormalities were discovered • Since cough can be simultaneously caused by more than one condition, do NOT stop therapy that appears to be partially successful; rather, sequentially add to it.
21Case Scenario 1 55 yo school teacher c/o cough for 3 years Non-smoker Cough: Often productiveBetter with abx, but comes back“no better” with asthma medsWorst in the morningFrequent clearing the throat, sensation ofdripping into throat
22Case Scenario 1 Nasal voice, afebrile, looks well Pharynx: Mild “cobblestoning”No facial tendernessNormal heart and lungsNormal spirometry
25Upper Airway Cough Syndrome Also called “Post-nasal drip syndrome” (PNDS)Common cause of chronic cough in all age groups– Second most common cause in children– Most common cause in adults and the elderlyIn addition to cough, UACS can also cause- Wheeze- Dyspnea
26Upper Airway Cough Syndrome Clues to UACS– History of• Need to frequently clear their throat• Friend/relative notices that the patientfrequently clears their throat• Sensation of dripping into throat• Nasal symptoms– Physical Exam demonstrating• Secretions in nose or oropharynx• Cobblestone appearance of mucosa
27Upper Airway Cough Syndrome Diagnosis of UACS as a cause of cough is established when:frequent throat clearing is elicited from the historyb) cobblestoning and phlegm are present onphysical examination of the posterior pharynxc) cough responds favourably to specific therapyaimed at eliminating the drip
28Treatment Antibiotics – sinusitis Oral antihistamine/decongestant x 3 weeksIntranasal decongestant for maximum of 5 days: e.g. oxymetazoline 2 sprays each nostril bid x 3 days only
30Case Scenario 2 The Computer Programmer, 35 y.o woman c/o Yearly cough lasted for > 8 weeks– starts only after a “cold weather” at end ofthe year– severe coughing– goes away by itself– has happened last year- nocturnal cough• Tried “everything”
31Case Scenario 2Denies: wheezes, PND sx, allergies, heartburn, aspiration• No: pets, current meds• Family hx: negative• PMH: negative• Physical exam and CXR normal• Normal spirometryAny other Ix?Methacholine Challenge Testing
32Asthma Second most common cause of cough in adults • Clues that chronic cough is due to asthma:– Episodic wheezing, dyspnea , cold or exerciseinduced– Reversible airflow obstruction– Bronchial hyperresponsiveness• Confirmed by resolution of cough with asthma treatment
33Cough Variant Asthma• 30-60% of patients presenting with chronic cough that was due to asthma had cough as their ONLY symptomClues:- nocturnal cough, exercise induced, after allergenexposureBronchoprovocation test: positiveNegative test exclude asthma but does not rule out steroid responsive cough
34ASTHMA/Cough Variant Asthma Treatment• Inhaled corticosteroid• ICS/LABA combination > 8 weeksLeukotrine receptor antagonist-Confirmed by resolution of cough with asthma treatment
35Non-Asthmatic Eosinophilic Bronchitis (NAEB) Eosinophilic airway inflammation WITHOUT variable airflow obstruction or airway hyperresponsivenessDiagnostic tests:Spirometry: normalMethacholine challenge: normalSputum or BAL eosinophilia: >3% eosinophilsDiagnostic/Therapeutic trial: inhaled corticosteroid for ≥ 4 weeksCharacteristically resistant to bronchodilator but reponds ICSConfirmed diagnosis if responded to ICS
36Case Scenario 2 The Computer Programmer… • Aggressive asthma regimen x 8 weeksNot feeling betterNow what??
37GERD Suspect GERD when… – Symptoms of heartburn or sour taste in mouth – Reflux demonstrated by• 24-hour pH-impedance monitoring• Barium x-ray• Cough is the only symptom of GERD in 40-75% of patients with chronic cough due to GERD
38GERDCough due to GERD occurs most commonly while patients are awake, stooping posture, meal related, and usually does not occur during the night• Diagnosis of GERD as cause of chronic coughrequires resolution of cough with GERD treatment
40TReatmentConservative measures : • Antacid therapy ≥ 2 months : – Proton pump inhibitor (high dose) – H2 blockers less effective • Motility therapy: – Metoclopromide Surgery is last resort
41ACE-inhibitor therapy Angiotensin converting enzyme (ACE) inhibitors (enalapril, captopril, lisinopril, ramipril, etc.)Dry cough in 3-30% patientsBegins 1 week to 6 months after drug startedUsually resolves 1-7 days after stopping therapy, but can take 4 weeksDiagnosis is confirmed when cough disappears after drug in discontinuedMinority of patient will have persistent cough even after the medication was off
43Fibreoptic bronchoscopy – biopsy High Resolution CT scan: lung parenchymal disease or bronchiectasis (not appreciated from hx and CXR)
44Case scenario 3Hamid, a 45 year old gentleman who is a clerk presented to the outpatient clinic after coughing up 2 cups of bright red blood.For the past 2 months, he has chronic cough productive of whitish mucoid sputumPrior to this episode, he had, on two occasion a blood-streaking on his sputum. He has also noticed that over the last few weeks he tires easily and is short of breath whenever he exerts himselfHemoptysis pulm origin: frothy sputum, absence of brownish-colored blood due to hemoglobin. a/w cough rather than vomitng. Usually blood is mixed with sputumNon pulm hemoptysis: dt aspiration of blood from nasal, oropharyngeal, gi or other bleeding site are brownish in colourPossible cause of hemoptysisLung caPtbBronchiectasisLVFPneumoniaPulmm infarction
45Case scenario 3 Further history.. Constitutional symptoms (fever, LOA, LOW)Fhx or contact with PTB patientSmoking historyOccupation and habitsOn direct questioning, he admit smoking 2 packs of cigarettes daily for the last 20 years but he has no known medical illness except for history of appendicectomy done 15 years ago. His appetite has been poor and he lost about 4 kg of his weight in 1 month , no contact with PTB paient.
46Case scenario 3Physical examination discloses a slightly apprehensive looking man who is not in acute distress.T: PR:100 bpm,regular, BP:130/80 mmHg and RR:17 per minuteSlight pallor but no cyanosis, no significant lymphadenopathy or finger clubbingAuscultation of the chest: generalized coarse crepitations but more over the right upper lobeCVS is normal with no signs of cardiac failureThere is no calf tendernessAt this point the most likely diagnosis is PTBWhat ix would u request
47Case scenario 3 Investigations: Full blood count ESR Blood C & S Mantoux testSputum AFB & cytologyChest X-rayECG
48Smear positive Pulmonary Tuberculosis Mantoux test is 12mmSputum: negative for AFBBronchoscopic washings :positive for acid fast bacilli
49Standard treatment regime: Intensive phaseGoal is to quickly kill the rapidly dividing organism to control disease and render patient non-infectious and prevent emergence of drug resistanceContinuation phaseSterilize the lungs by killing dormant and semi-dormant organisms to prevent relapseDOT allows for intermittent therapy
50Treatment of TUBERCULOSIS 2 months of daily EHRZ (2EHRZ)4 months of daily HR (4 HR)Dosage of 1st line anti-TB drugsIf ethambutol is contraidicated, streptomycin can be substituted
51TUBERCULOSIS Frequency Optimal Duration New patient with PTB: daily intensive regimen f/by daily maintenance regimenThrice weekly maintenance regimen can be considered under direct observationAll extrapulmonary: minimum 6 months except-- Bone and joint TB: 6 – 9months- TB Meningitis: 9 –12 monthsNo retrievable evidence on optimal duration of treatment for disseminated TB and miliaryTB -- should be low threshold to suspect TB meningitisWHO recommends daily dosing thorughout the entire treatmentHowever, a daily intensive phase followed by thrice weekly maintenance phase isan option provided that each dose is directly observed and patient has improved clinically.A maintenance phase with twice weekly dosing is not recommended since missing one dosemeans the patient receives only half the total dose for that week
52TUBERCULOSIS Follow-Up During & After Treatment Patients with initial sputum smear positive should have repeat sputum smear at two andsix months of antituberculous (antiTB) treatment. (Grade C)• Patients with initial sputum smear negative should have repeat sputum smear at twomonths of antiTB treatment. If still negative, no further sputum sample is required. (Grade C)• Patients who remains sputum positive at two months should be referred to specialist withexperience in tuberculosis (TB) management. (Grade C)• Sputum Mycobacterium tuberculosis culture and sensitivity testing should be obtained atthe start of antiTB treatment. (Grade C)• Chest x-ray should be performed at two and six months of antiTB treatment. (Grade C)• Follow-up within one month of starting antiTB treatment is advisable. (Grade C)• Follow-up may not be conducted routinely after completion of antiTB treatment. Patientsshould be well-informed on symptoms of TB recurrence. (Grade C)• Patients should be monitored for complications of antiTB drugs. (Grade C)
53Case Scenario 4 Tony is a bus conductor aged 45 years c/o recent exacerbation of his chronic cough with productive of yellow-green sputumHeavy smoker for 25 years. He has a long standing smoker’s cough frequently productive in recent years.Last year he suffered many exacerbation of his bronchitis, two of which were severe enough for him to be admitted to hospital.Although he had returned to work, progressive dyspnoea had made his job increasingly difficult
54Case Scenario 4Examination: drowsy, plethoric and cyanosed, flapping tremor was elicited.RR was 25/min, T: 38.2, PR: 124/min, regular rhythm, BP 120/80mmHgJVP raised 8cm, gallop rhythm was heard, sacral oedema present.Both lung fields had scattered crepitations and diminished air entry.The liver was felt 3 cm below the costal margin.No focal neurological deficit.
55CHRONIC OBSTRUCTIVE AIRWAY DISEASE SYMPTOMSShortness of breathChronic coughSputumEXPOSURE TO RISKFACTORSTobaccoOccupationIndoor/outdoor pollutionSpirometry should be performed after the administration of an adequate dose of a short-acting inhaled bronchodilator to minimize variability.A post-bronchodilator FEV1/FVC < 0.70 confirms the presence of airflow limitation.SPIROMETRY: Required to establish diagnosis
56CHRONIC OBSTRUCTIVE AIRWAY DISEASE An exacerbation of COPD is:“an acute event characterized by a worsening of the patient’s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication.”
57The goal of treatment is to minimize the impact of the current exacerbation and to prevent the development of subsequent exacerbationsArterial blood gas measurements (in hospital): PaO2 < 8.0 kPa with or without PaCO2 > 6.7 kPa in room air indicates respiratory failure.Chest X-Ray: useful to exclude alternative diagnoses.ECG: may aid in the diagnosis of coexisting cardiac problems.Full blood count: identify polycythemia, anemia, infectionPurulent sputum during an exacerbation: indication to begin empirical antibiotic treatment.Biochemical tests: detect electrolyte disturbances, diabetes, and poor nutrition.Spirometric tests: not recommended during an exacerbation.Antibiotics should be given to patients with:Three cardinal symptoms: increased dyspnea, increased sputum volume, and increased sputum purulence.Who require mechanical ventilation
58Oxygen: titrate to improve the patient’s hypoxemia with a target saturation of 88-92%. Bronchodilators: Short-acting inhaled beta2-agonists with or without short-acting anticholinergics are preferred.Systemic Corticosteroids:- Shorten recovery time, improve lung function (FEV1) and arterial hypoxemia (PaO2)- reduce the risk of early relapse, treatment failure, and length of hospital stay.mg prednisolone per day for days is recommendedNoninvasive ventilation (NIV):-Improves respiratory acidosis, decreases respiratory rate, severity of dyspnea, complications and length of hospital stay
59CHRONIC OBSTRUCTIVE AIRWAY DISEASE Indications for Hospital AdmissionMarked increase in intensity of symptomsSevere underlying COPDFailure of an exacerbation to respond to initial medical managementPresence of serious comorbiditiesFrequent exacerbationsOlder ageInsufficient home support
60Management of Stable COPD KEY POINTSIdentification and reduction of exposure to risk factors are important steps in prevention and treatmentIndividualized assessment of symptoms, airflow limitation, and future risk of exacerbations should be incorporated into the management strategyAll COPD patients benefit from rehabilitation and maintenance of physical activity.Pharmacologic therapy is used to reduce symptoms, reduce frequency and severity of exacerbations, and improve health status and exercise tolerance.Long-acting formulations of beta2-agonists and anticholinergics are preferred over short-acting formulationsLong-term treatment with inhaled corticosteroids added to long-acting bronchodilators is recommended for patients with high risk of exacerbationsLong-term monotherapy with oral or inhaled corticosteroids is not recommended in COPDThe phospodiesterase-4 inhibitor roflumilast may be useful to reduce exacerbations for patients with FEV1 < 50% of predicted, chronic bronchitis, and frequent exacerbationsAvoidance of risk factors- smoking cessation- reduction of indoor pollution- reduction of occupational exposureInfluenza vaccinationBased on efficacy and side effects, inhaled bronchodilators are preferred over oral bronchodilators.
61Global Strategy for Diagnosis, Management and Prevention of COPD Assessment of COPDAssess symptoms : CAT, mMRCAssess degree of airflow limitation using spirometryAssess risk of exacerbationsAssess comorbiditiesThe characteristic symptoms of COPD are chronic and progressive dyspnea, cough, and sputum production that can be variable from day-to-day.Dyspnea: Progressive, persistent and characteristically worse with exercise.Chronic cough: May be intermittent and may be unproductive.Chronic sputum production: COPD patients commonly cough up sputum
64Pharmacologic Therapy RECOMMENDED FIRST CHOICE GOLD 4ICS + LABAorLAMAICS + LABAand/orLAMA> 2GOLD 3Exacerbations per yearABGOLD 2SAMA prnorSABA prnLABAorLAMA1SAMA: short acting muscarinic agent = also called short acting anticholinergic e.g ipratropium bromide, o xitropium bromideLAMA: thiotopium, aclinidium bromideSABA: short acting B2 agonist : salbutamol, fenoterol, terbutalineLABA: Formoterol,SalmeterolICS: beclomethasone, budesonide, fluticasoneSymbicort: fluticasone + salmeterolCombivent: albuterol + ipratropiumPulmicort: budesonideSpiriva: tiotropiumProventil: albuterolAtrovent: ipratropiumGOLD 1mMRC 0-1CAT < 10mMRC > 2CAT > 10
65RehabilitationExercise training programs : improves exercise tolerance and symptoms of dyspnea and fatiguePulmonary rehabilitation program: the longer the program continues, the more effective the resultsOxygen Therapy: The long-term administration of oxygen (> 15 hours per day) to patients with chronic respiratory failure has been shown to increase survival in patients with severe, resting hypoxemiaVentilatory Support: Combination of noninvasive ventilation (NIV) with long-term oxygen therapy may be of some use in a selected subset of patientsLung volume reduction surgery (LVRS) : more efficacious than medical therapy among patients with upper-lobe predominant emphysema and low exercise capacityLung Transplantation : In appropriately selected patients with very severe COPD, improve quality of life and functional capacity
66Take Home MessageIn patients with chronic cough and a normal CXR finding who are nonsmokers and are not receiving therapy with an ACE inhibitor, the diagnostic approach should focus on the detection and treatment of UACS (formerly called PNDS), asthma, NAEB, or GERD, alone or in combination. This approach is most likely to result in a high rate of success in achieving cough resolution.ACCP Evidence-Based Clinical Practice Guidelines