Welcoming the Era of Pulmonglogy fl a and Critical Care in Internal Medicine s 6 INTRODUCTION gh is one of the most common symptoms Pr CH RONIG: q OUG fefuncer of chronic cough in clinical guidglanaghitad fuera Jor Bek (Durga NOTTS Nac US BENETA| OP Sd Skit Dalam RSHS~ Fk Unpad € of chroni¢cough eee in urope, America 10-20%) than itrAsia (<5% * Female > male — —~ 2-2anOv Te 2024 aINTRODUCTION * Cough is one of the most common symptoms * Reflex Protective, Cough can be a reflex or can be under volitional and cognitive control * The definition of chronic cough in clinical guidelines is cough persisting for >8 weeks ( Duration) NOT (Severity). * ~10% of adults in various general populations * The prevalence of chronic cough is higher in Europe, America and Australia (10-20%) than in Asia (<5%) * Female > maleGlobal prevalence of chronic cough ‘an Fan Chang, ea Cough Hypersenty a Chen Cough ae Revers. eae Primes rele Cation (022 B48Hi: ©08 + Istintemational guideline on cough + Summarized known physiology *+ Divided cough by duration: <3 weeks or 3-8 weeks ~Addressed common diagnoses and corresponding international guideline on cough, updating from ‘treatments for both categories 2006 + Neveraddressed truly chronic, inexplicable cough of>8 wk «Cough remains divided into same three durations: — duration Acute, <3 weeks eISeuonnonpasdianerbonelmimensremmamalte Sih tute 3.8 weeks per Cle Cea pes Coat HS) ISI Chronic, >8 weeks Again addressed common diagnoses and corresponding + 2nd international guideline on cough treatments Different disgnoss (and therefore “Now divi int three durations: Acule, <3 weeks __featments) in each category eee ee es Sa ‘Now known thatthe definitions were being used = Chronic, >8 weeks sunt pb ste poet slgriis ~ Again addressed common diagnoses and corresponding _-‘ Would accurately predict the mast common causes of treatments seule, subacute, and chronic cough.” ~ Different diagnoses (and therefore treatments) in each eared caneeonp npr itch pee category oval Dap ntact eohene ny ACP arte et los ht 2 gt 152382fi: 666 Terminology for chronic cough condition hetecoh Conhstig 3 weds Us oe valectin resiccoxh Cu asin > wes Fela Cenc cough CQ) oh pes ei atesing ale ras Mahe specs open capi hpenmey, Urpin esc cough CQ ‘Atm aed nicl vis Upland ro rete vasbat ray hae pepessimecie leah tapes ooh ype gone iar ractsedywatsne canting cn tggndy lowe teal edi Cescd ‘epeane oh tbe eae by seston cl be sor nesn phan ce com eh theron and cet mere, Lappe lyprsauily eral peetiy tag onda age lee ops fang ro eae lay cbsrucion ed Teghto bended y aad arta anes spon kerason yal soc, Parker SM, et al. Thorax 2023;6suppl 6):3~19Gi: ©66 The spectrum and frequency of chronic cough ProportionTHE SPECTRUM AND FREQUENCY OF RARE CAUSES OF CHRONIC COUGH BASED ON ANATOMY Anatomy Cases Upper inway (28, 1.636) SAS (2, 979%), mucous cst of savary land (1, 0.434), laryngocarcinoma (, 0.43%) VCD (2, 0.85%), lexyngeal amyloidosis (1, 0.43%) lower-airway (102, 5.796) PBB (44, 18.72%), DPB (31, 13.19%), FACC (4, 1.70%), bronchial tuberculosis (5, 2.13%), bronchial foreign body 2, 085%), ronhoitiass (1, 049%], BACC (1, 04%), Kenagner syndrome (1, 434), relapsing pelyhondits (8, 340%), sarcoidosis 1.043%), postoperative cough 1.70%) Lung @7, 15) ILD 3, 878%), sypicel preumocoros 2, (85%), COP 2, 085%) Other systems (78, 4.4%) Somatic cough syndrome (37, 15.74%), hyperventilation syndrome (15, 6.38%), ACEI-induced cough (8, 3.40%), arhiythmia (6, 2.13%), HIVD (3, 1.28%), goiter (1, 0.43%), occupational cough (2, 0.85%), styloid process syndrome (1, 0.43%), HES (31.28%), catamenial cough (1, 0.43%), LCH (1.043%), cardiogenic cough (104354)i: 666 * Chronic Cough SYMPTOM ,not "DISEASE” ICD System * Diagnosis and treatment challenging : Many pulmonary and some extrapulmonary diseases and disorders * 40% chronic cough referred for specialist foevaluation - No identified cause (unexplained chronic cough) - Persistent cough with optimal treatment ( refractory chronic cough) * Concept: Cough Hypersensitivity (Triggered by low levels of thermal, mechanical or chemical exposure) Morice, A. H. et al. 2014,ERS.QUALITY OF LIFE (QoL) * Significant effects on physical and mental health : uri sleep disturbance, interference of social situations and inabilit inary incontinence, pain, with speech, anxiety and depression, avoidance ity to work * Less common syncope and head injury, hernia, suicidal ideation and rib fracture * QOL can be assessed informally in the clinic by asking patients about the effects that are known to be associated with cough. * HRQOL questionnaires can be used to quantify QOL in a validated and standardized manner * The Leicester Cough Questionnaire is the most widely used HRQOL tool in adults. This tool consists of 19 items that address physical, psychological and social domains.===, eos 2024 APPENDIX 2: Scoring of LCQ (0) euler: sie fda ses ge 23)‘APENDI eer Cough Quesonnae, © 2001 aqnonie it ded esehe npasleaghanonas apa crore ted cen coe codes by CHONG a ern lbp yrs Pao nl gong hones eye eel Pecslonpitdeteceatpncamad rend! 2in las hom yo teenbheed yi ge otconntenyreaght Loe hae ante ae eh ‘Line lavas oeyas bended ht Abele 2a tonya ttecoeddierca Stored beso dina ocace ‘ute? we, myceintaleton Idee Hardie gmttdrae Sewdnire —hietene inales wes ey euphbsintend theyre} els {ntle2el tere uid teem erat Idmve — Herdtime —Teststere etter hadnt Saherdtene tends ‘bela wala epanet patiethmerbanetene gh amin taste tot Snetmre tates _tehondtere tdiHk O66 RISK FACTORS * Various environmental and host factors, respiratory infection, air pollutants, occupational irritants, allergens, eosinophils or refluxate * Patient factors. Age and sex underlie the burden and prevalence of chronic cough two-thirds of the patients female * Clinical factors.2024 @06 te); oll Ni(e-V8 * Cigarette smokers * Infection with respiratory viruses : severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 10-20% of patients after SARS-CoV-2 * Infection with Bordetella pertussis may also be associated with a prolonged cough (whooping cough). * Common pulmonary causes of chronic cough in non-smokers with normal chest X-rays and spirometry are corticosteroid-responsive cough such as eosinophilic conditions, ( cough variant asthma, non-asthmatic eosinophilic bronchitis and atopic cough * Chronic obstructive pulmonary disease (COPD), bronchiectasis, lung cancer, interstitial lung disease and obstructive sleep apnoea are also associated with chronic cough and cough hypersensitivity but chest radiology and/or lung physiology measurements are usually abnorma|* Extrapulmonary conditions : - GERD ~ Upper airway cough syndrome (‘post-nasal drip syndrome’) due to rhinitis or rhinosinusitis * Cough variant asthma,eosinophilic bronchitis,upper airway cough syndrome and GERD account for 51-92% of cases of adult chronic cough globally. * Adverse effect of angiotensin-converting enzyme (ACE) inhibitors,* Occupational irritants such as fumes, gases, cleaning products or dust may cause cough, either by triggering cough reflex or by inducing oxidative stress and eosinophilic inflammation * Air pollution is an important risk factor for chronic coughNeurophysiology of the cough reflexeral and central ‘ocesses contributing to cough hypersensitivity. (1) Precinia ties have described potential mechanisms ‘tha affect aga sensory nerve fibres that are driven bythe inflammatory pathology of the underlying clseases and potently reversed by disease-specific therapy. (2} Functional synergy ay ao exist between sensory neurons lneratng the various tsues shown Thee nteratons ely ‘occur atthe level of the brainstem, where convergence of ‘vagal and/or trigeminal Inputs leads to enhanced cough sanity, Peripheral gan pathologies have also been shown twalter synaptic efeacy inthe bralnster, Indicative of tate of ‘central sensization. Patients with cough ‘ypersensitty have (3) increased act in midran ares, ‘and €) a reduced ability to suppress coughing oningtoa fede to recruit descending brain networks that subserve cough suppression. (5) Patients with chronic ough havea range of efectsin the cognitive domain, suggestive of altered centcal processing of aireay sensory information, Orgs that target vagal sencery neurons ad inhibi thelr activity, nevromadulatory drugs that target bran proceses Involved In ‘mantaining hypersensitive states, and speech and language ‘therapy aimed at improving cough conto areal cially useful attussie options fr patients with troublesome cough. ‘NonFan Chung etl Coup Hypeentiey na Revews Dera PreEz OB =eH AND THE NERVOUS SYSTEMNeural pathways and mechanisms that contribute to the generation of cough.Cnforting OM0-19 axed cohandthe pa COND drome ofvinlneuctpim,i: ©O68 Management * Prolonged and complex, * Multiple comorbidities requiring treatment * Refractory to such interventions. * Therefore, management includes * Treatment of comorbid conditions that are potentially driving chronic cough * Therapies directed at cough hypersensitivity in patients with refractory or unexplained cough.Treatable traits of chronic cough sian | . ik: ©O8 =s ea at* Asthma Increasing inhaled corticosteroid dose and considering trials of leukotriene inhibitors and B-agonists The use of inhaled corticosteroid is considered the first-line treatment in adults with cough variant asthma. * GERD. Treatments for GERD include proton pump inhibitors (PPIs, which reduce the acidity of refluxate), histamine (H2) receptor blockers (which have a similar, but more prolonged, effect to PPIs) and lifestyle measures such as weight loss, elevating the head of the bed and avoidance of eating before bedtime. * Upper airway cough syndrome. The treatment of patients with chronic cough and nasal disease is standard care for the diagnosed nasal condition. Allergic or nonallergic rhinitis is treated with nasal corticosteroids, first or second generation and intranasal antihistamines, decongestants and, if sinusitis is present, antibiotics * COPD, Bronchitis chronic, bronchiectasis and interstitial lung disease. DISEASE SPECIFIC THERAPIES~ Treatable Traits = __ Chronic Coughi: OB RS Guideline on the diagnosis and treatment of chronic cough ‘thma Inhaled contort fist ne there enna ecmmendatin, ow ult eden. rpc ils west ‘hat higher doves ofS may be mre eet than low to moderate doves, Hower, he ul shoud be dscontned fn reponse sobre win 214 wees. etzapssts maybe coneredinconbraton WHI. cS are the refered inal weatment option (condonal recommendation low qualy ecdencl the air doesnot show adequiteimgronmen the dose shoul beincrened fr 24 wees ada lettin nile sold be considered a+ doa therapy, The empl should be continued if no resposeiseled win 2104 wees, ‘The bene ofan ad 2 atgois) ar pron pu inion (Ps for ough el patent witha rf ae ied ‘helmprovement sony min those wth ad eli (odtonal recommenda, low-qaiyedence. patents wih chvenic bronchi anda peste cough a Lonth il of maces maybe coniered whe adhere tlocal antici stewardship pies (condo econmendtin low-quality edene). lial estents for ale UAC inv rasa carters or atisanins For patents wih ACS websted eres, such as pstnecton the ole geeaton of athistamines held be andere fuk recommend, wilt) India wt sarclc reted cough my bene rom a weanert plan ching ol concseros owed by KS. Hower, corners mt be ndisied a patie with coh secon low eee, wea reconmendatns). ‘econmended if ow dest, slow ease mrp (to 10 eee ay (roe reammendain madera qsty ‘dene. Atif penn or pean ao econmende ids bo seek oni orate nile oleate ‘medations that conan ops (onto recommenda low quay eee Gabapentin uly tated wth dy dese 30 me, goby ceing wnt ough reel ade eles, oa mai dor of 00m per ayn ves ieached hi ah rnd a mane ee na renee sateen asNONSPECIFIC PHARMACOLOGICAL THERAPIES * Pharmacological therapies directed at eliminating cough are required in cases in which treatment of comorbid disease associated with cough is unsuccessful at relieving coughing, or in those with no obvious cause for a chronic cough. + Opiates. Codeine and morphine are commonly used antitussives in adult-based clinical practice and have antitussive effects via central opioid receptors169. Accordingly, effective antitussive doses of opiates are likely to cause sedation. + Codeine has a rapid onset of action, Morphine is ~10 times mor e potent than codeine andis most often considered in patients with severe intractable cough. + Gabapentinoids. The GABA derivatives gabapentin and pregabalin are inhibitors of a26 subunit- containing voltage-dependent calcium channels and possibly NMDA receptors + Tricyclic antidepressants. Amitriptyline increases noradrenergic or serotonergic neurotransmission by blocking presynaptic noradrenaline or serotonin transporters and has strong binding affinities for a-adrenergic, his-tamine (H1) and muscarinic (MI) receptors + Novel therapies « the positive effects of a P2x3 antagonist gefapixant however, disturbances in taste are a commcant 4 OOOOH MH £285 Ser 2888 Seas Seoansizecaa Safety, Pharmacodynamics and Pharmacokinetics of PDX Receptor Antagonist Eiapnan (BAY 1817080) in Healthy Subject: Double Bind Randoized Study Serre ee tee oe cst tt Satins nanamend::@08 ASSESSMENT OF COUGH IN ADULTS ‘Cough assessment in aduls. ACE: angiolensin-convering enzyme; CT: computed tomography, CXR: chest-x-ray, GERD: Gastroesophageal disorder, Cough wees “Galea 2twes tl ‘Acute [Subacite Chronic Symptomatic therapy ‘Riskfators: factrs* Ace inhib GERD symptoms Postal p SA [stone ‘Additional eval: Abnormal Normal Abnormal Bood{sputum osinophis | — T T Methacholine cal tales | 5) (naa [en ad etm net tad dua tnet ets ntehed anette atEvaluation and atc tet @O Management2024 MANAGEMENT OF COUGH HYPERSENTIVITY [ PHARMACOLOGICAL TREATMENT NEUROMODULATOR THERAPIES * Gabapentinoids Gabapentin improved cough-specific Qo Gabapentin should be started at a low dose, for example, gabapentin 100mg three times a day and then titrated up to a maximum dose of 600mg three times a day depending on clinical effects and side effects. Pregabalin 25mg two times per day intial and increase In increments to 75mg two times per day, Baclofen A single study of low dose amitriptyline (10mg once daily) reported significant improved cough over a combination of codeine/guaifenesin OPIOIDS (Efects via Central Opioid Receptor) * Morphine : Low-dose slow-release morphine sulphate S-10mg two limes per day * CodeinTT OF COUGH HYPERSENTIVITY NON-PHARMACOLOGICAL TREATMENT Speech and language therapi o Education o Cough control and suppression techniques o Breathing exercise o Vocal hygiene o CounsellingHE: ©6 ‘SPEECH AND LANGUAGE THERAPY MANAGEMENT OF CHRONIC COUGH The approach to cough-specifc speech and language therapy involves four steps. + Education Patients are provided education onthe biology of coughing, chronic coughand cough hypersensitivity and the negative effects of repeated coughing and throatclearingare explained. * Vocal hygiene. Vocal andlaryngeal hygiene and hydration are advised witha reduction in caffeine and alcohol intake. Nasal breathing with nasal douching may be recommended with nasal steam inhalation. * Cough control/suppression training. Following identification of patient cough triggers, patients are taught a range of suppression strategies including forced/dry swallow, sipping water, chewing gum or sucking non-medicated sweets. Breathing pattern re-education is used to promoterelaxed abdominal breathing whileinhaling through the nose, + Psycho-educational counselling. Behaviour modifications usedtoreduce over- awareness of theneed to cough and facilitate an individual's internalization of control cover theircough and tohelp manage stress and anxiety.a i ©68 Thankyou i