만성기침의진단 계명대학교의과대학내과학교실 기침은호흡기의사는물론이고일차진료의사가가장흔히접하는증상 1) 이나그원인에는경한감기증상으로부터폐암등의심각한질환의증상이기도하여가볍게대할수없는증상의하나이기도하다. 진단에있어서도문진및진찰소견만으로쉽게진단이되는질환도있고여러가지복잡한검사를하

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대진 승
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1 만성기침의진단 계명대학교의과대학내과학교실 기침은호흡기의사는물론이고일차진료의사가가장흔히접하는증상 1) 이나그원인에는경한감기증상으로부터폐암등의심각한질환의증상이기도하여가볍게대할수없는증상의하나이기도하다. 진단에있어서도문진및진찰소견만으로쉽게진단이되는질환도있고여러가지복잡한검사를하여도진단이확실하지않아서의심되는질환들을배제시킴으로써또는치료에대한반응을평가함으로써진단이가능할때도있다 2). 또기침의원인이단일질환일수도있지만기관지천식과위식도역류가같이있거나후비루와기관지천식이같이있는등의한가지이상의질환이원인이되기도하여한가지질환을치료하여서는치료효과가좋지않은경우도있을수있다. 기침의원인이다양하기때문에진단적접근에있어서가장기본적으로사용되는것이첫진료시까지의기침의지속기간에따른분류이다 3). 일반적으로급성기침은지속기간이 3주이내인경우이며그원인으로는감기, 알레르기성비염, 급성세균성기관지염, 만성폐쇄성기도질환의급성악화등이흔한원인이며, 아급성기침은 3주에서 8주정도지속되는기침을말하며그원인으로는감염후 (post-infectious) 기침, 기관지천식, 아급성세균성부비동염이흔한원인이고, 만성기침은 8주이상지속되는기침으로분류한다 3,4). 그러나급성, 만성으로만구별할때는 3주이상지속되는기침을만성기침으로정의하기도한다. 대체로감염후기침은 2개월이내에저절로호전되는경우가많으며 3) 임상에서진단에어려운점이많은경우가대부분만성기침이므로여기에서는면역결핍이없는성인의만성기침의원인과진단및치료에대하여기술하고자한다.

2 ( 그림 1).

3 Table 1. Major causes of chronic persistent cough in adults* Post-nasal drip syndrome (PNDS): the most common Asthma Gastroesophageal reflux disease (GERD) Nonasthmatic eosinophilic bronchitis Angiotensin converting enzyme inhibitor (ACEI)-induced cough Miscellaneous bronchitis Chronic bronchits Bronchiectasis Interstitial lung disease *with normal chest radiograph 만성기침의진단에있어서병력및진찰소견외에가장기본적인검사가흉부사진촬영이되는데만성기침의원인중흉부사진상정상소견을보이거나정상에가까운흉부사진또는일정기간동안변화가없는소견을보이는경우의가장흔한원인으로는후비루, 기관지천식, 위식도역류질환이며담배등의자극성물질에의한만성기관지염, 기관지확장증, 호산구성기관지염과안지오텐신전환효소억제제부작용등이만성기침의약 95% 를차지한다 2-4) ( 표 1). 흉부사진이정상소견이면서만성기침을일으키는나머지 5% 의원인으로는폐암, 전이성폐암, 폐결핵, 좌실실부전, 인후장애에의한흡인, 간질성폐질환등이있으며기관또는기관지결핵도그원인일수있다 5-7). 만성기침환자의진료에있어서피해여야할사항중의하나는기침의원인이심인성또는습관성이라고진단하는것이다 4). 이렇게진단된환자의대부분이후비루나기관지천식, 위식도역류질환또는호산구성기관지염이원인일수가있기때문에환자의주거및직장환경에대하여주의를기울여야한다. 실제로치료가잘안되어호흡기의사에게의뢰된환자의적어도 23% 가심인성기침이라고진단을받는다는보고도있다 8). 특히야간에는기침이없다거나기침의양상만을보고심인성이라고진단하는것은근거가없다고한다 9). 또만성기침은환자에게여러가지다양한사회적, 정신적인영향을줄수있으며심인성인기침보다는오히려만성기침에의해서정신적인문제가생길수있다는점을유념하여야한다 10). 또한가지이상의원인이있는경우도비교적흔하므로 (18~93%) 어느한질환에대한치료에조금호전을보인다고하여한가지원인만을생각하여서도치료에실패하는원인이될수있다 2).

4 만성기침의원인중가장흔한원인이며대부분비강분비물이목으로넘어가는느낌이있거나자주목에가래가붙어있어서자주의도적으로기침을하여떼어낸다거나, 콧물이자주나고내시경소견상구인두에점액이붙어있거나점막에변화를보이는등의소견을보이는경우가흔하지만이런소견이전혀없는경우도있으므로성급하게가능성을배제하여서는안되며치료에대한반응을관찰하여야한다 11). 또후비루의증상이있어서치료한경우반응이나쁘다면위식도역류에의한증상도비슷할수있으므로고려하여야한다 8,12). 후비루의원인질환으로는통년성비염, 알레르기성비염, 혈관운동성비염 (vasomotor rhinitis), 부비동염등이있다. 부비동염의진단에는부비동 CT 촬영이가장민감한검사이지만흔히이용하는부비동촬영만으로도대부분충분한소견을얻을수가있다 13). 그러나진찰소견과부비동촬영소견으로는진단이힘든경우가많기때문에후비루치료에대한반응을관찰하는것이무엇보다도움이될수있다 2). 후비루의치료는그원인에따라서다르지만비알레르기성비염에는 1세대항히스타민제, 충혈완화제등을약 3주정도상용하면호전을보이므로진단에도움이되며화농성부비동염인경우는그원인균즉, 혐기성균이나 H. influenzae에잘듣는항생제를사용하여야한다 4). 새로개발된항히스타민제가많이있지만중추신경부작용은감소되었으나비알레르기성후비루증상완화에는오히려 1세대항히스타민이더효과적인데그이유는기침중추의억제효과외에항콜린성효과때문으로생각된다. 그러나녹내장이나전립성비대증때문에항히스타민제를사용할수없는환자에게는비강용항콜린제가도움이된다 2). 혈관운동성비염에는항콜린제의비강도포가도움이되며알레르기성비염에는원인알레르겐을피하는것외에 loratidine과같은항히스타민이도움이된다 ( 표 2).

5 Table 2. Guidelines for treating the most common causes of chronic cough in adults Cause Therapeutic Options Comments Postnasal-drip syndrome Nonallergic rhinitis Allergic rhinitis Vasomotor rhinitis Chronic bacterial sinusitis Asthma GERD ACEI Eosinophilic bronchitis 1st generation H 1 antagonist + pseudoephedrine for 3 w, or ipratropium nasal spray for 3w Avoidance of offending allergens Loratadine, 10mg once a day Ipratropium nasal spray for 3 w 1st generation H 1 antagonist + Pseudoephedrine for 3 w, Antibiotics against H. influenzae, S. pneumoniae, and anaerobes Steroid inhaler±β 2 agonist inhaler Modification of diet and lifestyle Acid Suppression. Prokinetic therapy Discontinuation of drug Steroid inhaler for 14d Nasal steroid spray or 2nd generation H 1 antagonists will probably yield poorer results Other H 1 antagonists, nasal cromolyn. Steroid and azelastine may be helpful. 3 w of antihistamine, decongestant and antibiotics. After cough resolves, nasal steroid for 3 m. Initial medial therapy should be intensive (dietary changes, protonpump inhibitor and prokinetic drugs) If no improvement in 3 m, 24 h-ph monitoring is needed. With discontinuation, cough should improve or resolve within 4 w. No cough with angiotensin II-receptor antagonist Systemic corticosteroids (prednisone, 30mg/d for 2~3w)are sometines required Table 3. Suggested diagnostic and therapeutic trials in chronic cough Possible Etiology Asthma Postnasal drip GERD Diagnostic or Therapeutic Trial Pulmonary function tests with methacholine challenge Trial of inhaled bronchodilators Nasal endoscopy Trial of long-acting decongestant/antihistamine Ambulatory ph test Therapeutic trial of proton pump inhibitors 기관지천식의기침은발작적이라고하지만그특징이별로없어서진단에는도움이되지못하며천명음과호흡곤란이없이기침만을가진기침변이성천식 (cough-variant asthma) 은진단이쉽지않을수있다 9,14). 그러나야간, 특히새벽 2~4시경에심하다던지, 천명음을동반하거나계절에따른변화가뚜렷하다면천식의가능성이높아지게된다. 그리고메타콜린유발검사가음성이라면천식의진단을배제할수있기때문에다른원인을찾아야한다 ( 표 3). 그러나상기도감염후에도이검사가양성으로나올수있으며천식외에도양성반응을보이기때문에양성추정율은 60~82% 정도로알려져있다 2). 기침변이성천식의치료는일반적인천식치료와동일하여대체로흡입용스테로이드나베

6 타-2 자극제에잘듣는편이며기침때문에흡입제사용이어려운경우는전신용스테로이드를사용한다 2). 만일상기한치료에반응이없으면메타콜린양성반응이위양성일가능성을생각하여야하며드물게는조절난해성천식일경우도고려해야하나이경우위식도역류가동반되어있을수있으므로이에대한검사및치료도병행하여야할경우도있다 16, 17). Table 4. Clinical profile of patients with cough due to "silent" gastroesophageal reflux disease Patients will: Complain of a dry or productive cough for a duration of at least 2 mo Not be immunocompromised Have a normal or near-normal chest radiograph that shows nothing more than stable and inconsequential changes Not be smoking or be exposed to other environmental irritants Symptomatic asthma has been ruled out; Methacholine challenge is negative, or Cough has not improved with asthma medications Postnasal drip syndrome due to rhinosinus diseases have been ruled out; First-generation H 1-antagonists have been used and failed to improve cough, and "Silent" sinusitis has been ruled out Eosinophilic bronchitis has been ruled out; Properly performed sputum studies are negative, or Cough has not improved with inhaled/systemic corticosteroids Table 5. Respiratory signs and potential pulmonary manifestations of GER Respiratory signs of GER Hoarseness, especially in the morning Repeated need to clear the throat Sensation of pressure deep in the throat Chronic persistent cough Nocturnal or early morning wheezing Hyperventilation Laryngeal spasm GER, gastroesophageal reflux Potential pulmonary manifestations Chronic asthma Bronchitis Bronchiectasis Aspiration Pneumonia Atelectasis Pulmonary fibrosis Laryngitis 위식도역류질환은만성기침의 3대원인중의하나이지만진단과치료에있어서여러가지어려운점이많이있는질환이다 2). 그것은기침의특징이나시간적인상관관계가확실하지않고 9) 위식도역류의 75% 가증상이없는무증상위식도역류 (silent GERD) 이기때문이다 16). 가슴앓이 (heart burn) 증상이나위내용물의역류증상이있고특히흉부사진상흡인의소견이있으면더확실하지만, 흉부사진이정상소견이면서위, 식도증상이없더라도만성기침의원인으로후비루나기관지천식, 호산구성기관지염이배제된다면위식도역류질환이만성기침의원인으로고려되어야한다 4) ( 표 4). 특히취침후목소리가변한다든가인후에이물감이있어서자주목청소 (throat clearing) 를하고목이답답하다는느낌이있으면후비

7 루외에도역류질환을의심하여야한다 12,17,18) ( 표 5, 그림 2). Classic (heartburn, regurgitation) Atypical Extraesophageal Complications esophagitis non-erosive GERD chest pain hiccups dyspepsia chronic cough asthma chronic hoarseness stricture bleeding night sweats (laryngitis) Barrett's dyspareunia aspiration pneumonia esophagus globus? erosion of dental enamel Figure 2. Spectrum of gastroesophageal reflux disease (GERD) 위식도역류시기침을일으키는기전으로는위내용물이호흡기로흡인되어직접기도를자극하여생기기도하고식도로역류되어올라온위산이미주신경반사기전을통하여기관지를자극하는것으로알려져있다 17). 진단에는 24시간식도 ph감시가가장민감한검사방법이지만침습적인방법이고보편적으로시행할수있는검사가아니며특이도가 66% 정도밖에되지않기때문에 2,17) 먼저 2~3개월정도치료를시도하여보고반응이만족스럽지않으면 24시간식도 ph감시를추천하기도한다 2,4). 또식도내의산도가위식도역류에의한기침의주된원인이아니라는보고 14,18) 도있기때문에역류를증명한다고하여이것이반드시만성기침의원인이라고할수도없다. 치료로는체중과다인경우는체중을줄이고취침전 2시간내에는식사를피하는등의생활습관변화와 proton pump inhibitor, H2-blocker, prokinetic drugs를사용하는데증상호전에걸리는시간이보통 2~3개월이소요되며 7) 5~6개월정도치료하여야기침이완전이호전되므로충분한기간동안사용하여야한다 6,8). 또역류를일으킬수있는약제, 칼슘길항제, nitrate, 프로제스테론등을같이사용하는경우는조절이힘들수있으며 17) 폐쇄성무호흡이있는경우도치료가어렵다 19). 상기치료로서치료가되지않는경우는수술적치료 (antireflux surgery) 로서역류증상을개선시킬수있다 20-22). 이질환은 1989년 Gibson 등 23) 에의해서기술되었는데천식과같이기도나객담에호산구가증가 ( 비편평상피세포의 3% 이상 ) 하는질환으로천식과의차이점은기관지과민성이나기관지폐색의변이성이없다는점이다 24). 이질환은만성기침의원인중약 13% 까지보고 15) 되고있는드물지않은질환으로메티콜린유발검사에음성을보이나스테로이드치료에반응을잘하는특징을가지고있다 24). 원인은잘알려져있지않았는데아토피성, 비아토피성모두에서생길수있으며흡연유무와도무관하게생길수있고직업과관계된화학자극물질 ( 레진, 알레르겐 ) 노출과도관계

8 가있다는보고가있다 24). 치료는흡입용스테로이드를사용하면효과가좋으며반응이적은경우는전신성스테로이드를사용하기도한다 23). 최근에치료가잘되지않으면비가역적인기도폐색을일으킬수있다는보고도있다 25). ACEI 유발성기침은이약을복용하는환자의 10% 정도에서발생하며목이간질거리는느낌과심한마른기침이주된증상으로서폐기능과는무관하다. 그러므로천식환자에서더많이나타나지는않는다. 기침이나타나는시점은약복용후수시간에서수주내지는수개월후에나타나며약을중단하면호전되나완전히소실되는데는약26일간의시간이걸린다 26). 약제의용량과는무관하게발생하며다른종류의약제로바꾸어사용하여도증상이별로개선되지는않는다 2). 그러나 losartan과같은안지오텐신 II 수용체길항제로바꾸면기침이호전된다 26). 기전은안지오텐신변환효소억제제 (ACEI) 가기관지조직내에 bradykinin, substance P를증가시키고, pro-staglandin을증가시킴으로써기침반사의민감도를증가시켜서생기는것으로생각되며 2,26) nifedipine같은칼슘길항제나인도메타신과같은약제는 prostaglandin의생성을억제함으로써기침을감소시키는것으로보아이기전을뒷받침하고있으며 ACEI를사용하여야하는환자는이들약제외에흡입용크로몰린을같이사용하면도움이된다 2,27). 진단은검사방법이없으면이약제를사용한후기침이나타났다면반드시이약제를중단하고기침이호전되는지를관찰하여야하며기침이호전되는데는약 4주가소요된다 2). 기관염, 기관지염, 세기관지염과기관지확장증등의화농성염증을일으키는질환도만성기침의원인이되는데화농성이라고하여반드시감염이원인이되지는않는다 2,4,28). 즉, 염증성대장질환에서도기도질환을보일수있으나 29) 대부분화농성객담을동반한기침을보이므로지금까지기술한만성기침의원인들과는구별이가능하며기관지확장증이의심되면고해상도흉부전산화단층촬영으로써진단이가능하다 4). 또상기한진단수기로서만성기침의원인진단이되지않을경우에는폐암이나성대기능이상을확인하기위한기관지내시경도고려되어야한다 30). 원인이알려지지않은특발성폐섬유증등과각종무기물또는유기물분진, 약제, 결제조 직질환등원인이너무나다양하며대체로마른기침과호흡곤란이주증상이며초기에는 흉부사진상정상소견을보일수있으나진찰소견상수포음이들리는경우가흔하며폐기능

9 검사상제한성환기장애와폐확산능감소의소견을관찰할수있다. 진단에는병력이무엇보다중요하며특히직업력, 약제복용, 취미및애완동물등에이르는상세한병력과피부, 관절등의다른장기의병변유무에도자세한관찰을요한다 31,32). 의심되면고해상도흉부전산화단층촬영이많은도움이될수있다 2). 만성기침은그원인이다양하나특징적인소견이별로없고진단방법에있어서도결정적인검사방법이없어서진단에있어서도결정적인검사방법이없어서진단에있어서어려운점이많은다루기힘든증상이다. 상세한병력이진단에필수적이지만특수한검사를시행하여야진단이가능한경우가있으므로때로는전문의에게의뢰하여야하는경우도있을수있다. 또치료에있어서도시간이많이걸리거나재발이잦은질환도있어서환자가의사의판단에따라오지않는어려움도있을수있다. 후비루, 기관지천식, 위식도역류질환이가장흔한원인질환이나진단이쉽지않아서때로는가장의심이가는질환에대하여충분한기간동안치료를하여그반응을보아야만진단이가능할수도있고, 또이들질환이한가지이상같이있는경우도드물지않기때문에면밀한주의를기울여야한다. 특히후비루와기관지천식, 기관지천식과위식도역류가같이있는경우가있기때문에염두에두고어느한질환의치료에반응이좋지않으면이러한원인을고려하여야한다. 비알레르기성비염의치료할때주의하여야할점은최근에는 2~3세대의항히스타민을많이사용하고있으나 1세대항히스타민보다효과가훨씬떨어지므로 1세대항히스타민을사용하여야치료효과를기대할수있으며위식도역류질환의경우에는처음부터 24시간식도 ph 측정을하는것이아니고의심되면역류에대한치료를하여그반응을관찰하도록권하고있지만상부위장관내시경소견등이첨부되지않으면 proton pump inhibitor와 prokinetic drug등의약제가건강보험의적용을받을수없는현식적인문제도개선되어야할사항으로생각된다. REFERENCES 1) Irwin RS, Madison JM. Symprom research on chronic cough: a historical perspective. Ann Intern Med 134: , ) Irwin RS, Boulet L-P, Cloutier MM, Fuller R, Gold PM, Hoffstein V, Ing AJ, McCool D, O'Byrne P, Poe RH, et al. Managing cough as a defense mechanism and as a symptom: a consensus panel report of the American College of Chest Physicians. Chest 114(Suppl):133S-181S, ) Irwin RS, Madison JM. The diagnosis and treatment of cough N Engl J Med 343: , ) Irwin RS, Madison JM. The persistently troublesome cough. Am J Respir Crit Care Med 165: , 2002

10 5) Palombini BC, Villanova CA, Araujo E, Gastal OL, Alt DC, Stolz DP, Palombini CO. A pathogenic triad in chronic cough: asthma, postnasal drip syndrome, and gastroesophageal reflux disease. Chest 116: , ) Irwin RS. Cough. In : Irwin RS, Curley FJ and Grossman RF, editors. Diagnosis and treatment of symptoms of the respiratory tract. Armonk, NY: Futura Publishing Company p ) Irwin RS. Zawacki JK, Curley FJ, French CL, Hoffman PJ. Chronic cough as the sole presenting manifestation of gastroesophageal reflux. Am Rev Respir Dis 140: , ) Irwin RS, Corrao WM, Pratter MR. Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcome of specific therapy. Am Rev Respir Dis 123: , ) Irwin RS, Curley FJ, French CL. Chronic cough: the spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy. Am Rev Respir Dis 141: , ) Mello CJ, Irwin RS, Curley FJ. The predictive values of the character, timing, and complications of chronic cough in diagnosing its cause. Arch Intern Med 156: , ) French CL, Irwin RS, Curley FJ, Krikorian CJ. Impact of chronic cough on quality of life. Arch Intern Med 158: , ) Pratter MR, Bartter T, Akers S, DuBois J. An algorithmic approach to chronic cough Ann Intern Med 119: , ) Theodoropoulos DS, Ledford DK, Lockey RF, Pecoraro DL, Rodriguez JA, Johnson MC, Boyce HW Jr. Prevalence of upper respiratory symptoms in patients with symptomatic gastroesophageal reflux disease. Am J Respir Crit Care Med 164:72-76, ) Pratter MR, Bartter T, Lotano R. The role of sinus imaging in the treatment of chronic cough in adults. Chest 116: , ) Pratter MR, Hingston DM, Irwin RS. Diagnosis of bronchial asthma by clinical evaluation: an unreliable method. Chest 84:42-47, ) McGarvey LP, Heaney LG, Lawson JT, Johnston BT, Scally CM, Ennis M, Shepherd DR, MacMahon J. Evaluation and outcome of patients with chronic non-productive cough rsing a comprehensive diagnostic protocol. Thorax 53: , ) Irwin RS, French CL, Smyrnios NA, Curley FJ. Interpretation of positive results of a methacholine inhalation challenge and 1 week of inhaled bron-chodilator use in diagnosing and treating cough-variant asthma. Arch Intern Med 157: , ) Irwin RS, Curley FJ, French CL. Difficult to control asthma: contributing factors and outcome of a systematic management protocol. Chest 103: , ) Irwin RS, French CL, Curley FJ, Zawacki JK, Bennett FM. Chronic cough due to

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<B0E6C8F1B4EBB3BBB0FAC0D3BBF3B0ADC1C E687770> 개원의와함께하는임상강좌 2011 역류성식도질환제대로이해하기 Division of Gastroenterology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea Jae-Young Jang, M.D., PhD. 개원의와함께하는임상강좌 2011 109 최신치료