DOI: 10.4046/trd.2010.69.5.368 ISSN: 1738-3536(Print)/2005-6184(Online) Tuberc Respir Dis 2010;69:368-374 CopyrightC2010. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved. Original Article 만성기침환자의주관적증상과비후두경소견및객담호산구증가증과의관련성 1 인제대학교의과대학해운대백병원호흡기내과학교실, 울산대학교의과대학서울아산병원 2 호흡기내과학교실, 3 알레르기내과학교실, 4 천식센터김현국 1, 최은영 2, 이재승 2, 배윤정 3, 송진우 2,4, 김태범 3,4, 조유숙 3,4, 문희범 3,4, 이상도 2,4, 오연목 2,4 Relation between Subjective Symptoms and Rhinolaryngoscopic Findings or Sputum Eosinophilia in Chronic Cough Patients Hyun Kuk Kim, M.D. 1, Eun Young Choi, M.D. 2, Jae Seung Lee, M.D. 2, Yun Jeong Bae, M.D. 3, Jin Woo Song, M.D. 2,4, Tae-Bum Kim, M.D. 3,4, You Sook Cho, M.D. 3,4, Hee-Bom Moon, M.D. 3,4, Sang Do Lee, M.D. 2,4, Yeon-Mok Oh, M.D. 2,4 1 Department of Pulmonary and Critical Care Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Departments of 2 Pulmonary and Critical Care Medicine, 3 Allergy, 4 Asthma Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Background: Rhinolaryngoscopy and sputum examination are popular tests for the evaluation of chronic cough. Little is known about the relationship between symptoms and rhinolaryngoscopic findings or sputum eosinophilia in chronic cough patients. Methods: One hundred patients, who had chronic cough with normal chest radiography and who also had undergone both rhinolaryngoscopy and induced sputum analysis, were reviewed retrospectively. Eleven associated symptoms of chronic cough were asked; postnasal drip (PND) and laryngopharyngeal reflux (LPR) were examined by rhinolaryngoscopy. Induced sputum analysis was performed for evaluation of sputum eosinophilia. Cross tabulation analyses with chi-square tests were used to evaluate the relationship between symptoms and objective findings. Results: The most frequent symptom was sputum (70%). The prevalence of PND and LPR on rhinolaryngoscopy were 56% (56/100) and 25.6% (22/86), respectively. Sputum eosinophilia was observed in 23 (23.7%) of 97 patients. The dyspnea (p=0.001), sputum (p=0.003), nasal obstruction (p=0.023), and postnasal drip sense (p=0.025) were related with PND on rhinolaryngoscopy. LPR on rhinolaryngoscopy was not related with any symptoms. Dyspnea (p=0.003), wheezing (p=0.005), nasal obstruction (p=0.013), and belching (p=0.018) were related with sputum eosinophilia. Conclusion: Any symptoms might not be related with LPR on laryngoscopy. Some symptoms might be related with PND on rhinoscopy or with sputum eosinophilia. Key Words: Cough; Chronic Disease; Rhinoscopy; Laryngoscopy; Sputum; Eosinophils 서 론 Address for correspondence: Yeon-Mok Oh, M.D. Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Pungnap 2-dong, Songpa-gu, Seoul 138-736, Korea Phone: 82-2-3010-3136, Fax: 82-2-3010-6968 E-mail: ymoh55@amc.seoul.kr Received: Aug. 11, 2010 Accepted: Oct. 3, 2010 8주이상지속되는만성기침은호흡기및알레르기진료실에서흔히접하는증상이다. 만성기침의흔한원인으로는이전에후비루증후군으로불리던상기도기침증후군 (upper airway cough syndrome), 기침형천식 (cough variant asthma), 위식도역류 (gastroesophageal reflux) 368
Tuberculosis and Respiratory Diseases Vol. 69. No. 5, Nov. 2010 등이있다 1,2. 각각의원인감별은쉽지않아환자가호소하는증상에따라원인을추정하고경험적으로약물투여를시도하는것이일반적이다. 그리고증상을통해서원인을추정할수없는경우에는상기도기침증후군, 기침형천식, 위식도역류순으로약물치료를시도해보거나부비동영상검사, 위식도내시경, 메타콜린반응검사등을시행한후에결과에따라서약물치료를시작할수있다. 만성기침의원인으로인후두역류 (laryngopharyngeal reflux) 라는질환이알려져있고위식도역류와는다른질환으로인식되고있다 3. 인후두역류는위장관관련증상보다는쉰소리, 목청소등의후두와관련된증상을나타내고위식도내시경검사에서식도염소견이흔하지않고진단을위해서는이중탐촉자를이용한 24시간 ph 모니터를이용해서상부식도의역류를확진할수있다. 인후두역류의진단은일차적으로증상과후두경소견으로이루어진다 4,5. 만성기침의진단에비후두내시경과유도객담검사는많은도움을줄수있으며비교적침습성이적어실제진료현장에서이용되고있다. 하지만현재까지만성기침환자에서시행한비후두내시경과유도객담검사에대한국내연구는많지않다 6. 본연구는만성기침환자의비후두내시경및객담검사를통한객관적소견과환자의주관적증상과의연관성을분석하여어떤증상이비후두내시경의이상소견및객담호산구증가와관련이있는지확인하고자하였다. 대상및방법 전담하여환자와면담하여얻었으며미리고안한증상문항을간호사가작성하도록하였다. 조사된증상은호흡곤란 (dyspnea), 쌕쌕거림 (wheezing), 객담 (sputum), 콧물 (rhinorrhea), 코막힘 (nasal congestion), 재채기 (sneezing), 후비루감각 (postnasal drip sensation), 목간지럼 (throat tickle), 속쓰림 (epigastric soreness), 구역 (belching), 가슴앓이 (heart burn) 등 11개였다. 비후두내시경은한명의알레르기내과전문의가전담하여검사하고결과를기술하였다. 비내시경은 MGB SINOLUX-telescope 2.7 mm/0 o (MGB Endoskopische Gerate GmbH Berlin, Berilin, Germany) 를사용하였고후두내시경은 MGB telescope 6 mm/70 o (MGB Endoskopische Gerate GmbH Berlin) 를사용하였다 (Figure 1). 환자의비강내에국소마취제를점적한후에환자를의자에반듯하게앉히고검사를진행하였다. 비강을관찰한후에내시경을바꾸어후두를관찰하였다. 후비루는비인두의점막표면에분비물이관찰되는경우에양성으로판단하였고정도가심한순서대로 1+ 4+ 로구분하여기술하였다. 본연구에서는임의적으로후비루의존재를 2+이상인경우로정의하였다. 인후두역류는후교련 (posterior commissure) 의비대가관찰되거나모뿔연골 (arytenoid) 점막의홍반성변화나부종이관찰되는경우로정의하였다. 객담호산구검사는유도객담의분석을통해이루어졌다. 유도객담의채취방법과분석방법은 Kwon 등 7 이보고한방법을사용하였다. 객담호산구증가증은유도객담에서 3% 이상의호산구가관찰되었을때로정의하였다. 본연구는후향적연구로서환자동의서취득없이연구 서울아산병원천식센터에 2008년 9월부터 2009년 3월까지 8주이상동안기침을주소로방문한환자 124명을스크리닝하여흉부단순촬영에서비정상을보이는환자를제외하고흉부단순촬영에서정상이거나의미가없어보이는경미한병변을보이는 100명의환자를대상으로후향적으로분석하였다. 흉부단순촬영에서의미가없어보이는경미한병변은국소적인섬유화나반흔등이었다. 대상환자중 6명은현재흡연자였지만병력에서흡연을최소 1개월이상중지한후에도기침이지속되어서대상에포함하였다. 안지오텐신전환효소억제제사용자는 6 명이었고모두기침발생전 5년이상약제를복용하던중이었다. 환자의주관적증상에대한병력청취는간호사한명이 Figure 1. Endoscopes for the evaluation of nasal cavity, pharynx and larynx. The upper endoscope has 70 angle at the tip and was used to examine the oropharynx and larynx. The lower one was used to examine the inside of the nasal cavity and nasopharyngeal mucosa. 369
HK Kim et al: Relation between symptoms and objective findings in chronic cough patients 를진행하는것에대해서서울아산병원임상연구심의위원회의심의를통과하였다. 통계적분석은교차분석을사용하였다. 통계프로그램은 SPSS version 17.0 (SPSS Inc., Chicago, IL, USA) 을이용하였다. p값은 0.05 이하일경우에의미있는차이가있다고판단하였다. 결 대상환자는여자 70명, 남자 30명으로총 100명이었다. 나이는 49±16세 ( 평균 ± 표준편차 ; 범위, 17 82세 ) 였다 (Table 1). 기침의지속기간은 59±90개월 (2 480개월) 이었다. 흡연상태는 80명이비흡연자, 6명은현재흡연자, 14명은과거흡연자였다. Table 1. Patient s characteristics No. of patients 100 M : F 30 : 70 Age, yr 49±16 (17 82) Duration of cough, mo 59±90 (2 480) Smoking status Nonsmoker 80 Current smoker 6 Ex-smoker 14 ACE inhibitor use 6 Values are expressed as mean±standard deviation or number of subjects. ACE: angiotensin converting enzyme. 과 전체기침환자중각각의주관적증상을호소하는환자는호흡곤란 29%, 쌕쌕거림 29%, 객담 70%, 콧물 46%, 코막힘 35%, 재채기 38%, 후비루감각 42%, 목간지럼 27%, 속쓰림 4%, 구역 9%, 가슴앓이 2% 등으로객담을호소하는환자수가가장많았다 (Figure 2). 호흡곤란을호소하는환자의 59% (17/29) 는쌕쌕거림을함께호소하였고 93% (27/29) 의환자는객담을함께호소하였다. 쌕쌕거림을가지는환자들의 93% (27/29) 또한객담을호소하였다. 환자들이호소하는주관적증상의개수는없는경우 6%, 1개 23%, 2개 13%, 3개 14%, 4개 8%, 5개 17%, 6개 17% 등으로평균적으로 3.3개의증상을기침외에호소하였다. 비내시경은모든환자에게시행되었고 56% 의환자에서후비루가관찰되었다. 그리고 9명의환자에서비중격만곡이관찰되었고 2명의환자에서는비용종이관찰되었다. 환자중에비강및비인두부관찰은가능했으나구역으로후두부위를관찰하지못한경우가있었다. 후두내시경을통해후두관찰이가능했던 86명의환자중에서 25.6% 의환자에게인후두역류가관찰되었다. 유도객담검사는 97명의환자에게시행되었고 23.7% 의환자에서객담호산구증가가관찰되었다 (Figure 3). 3명은유도객담을채취하는데실패하였다. 환자의주관적증상과비후두내시경및유도객담의객관적인소견과의관련성은다음과같았다. 비내시경에서후비루소견을보이는환자는후비루소견을보이지않는 Figure 2. Percentage of patients with each symptom among all of the chronic cough patients. PND: postnasal drip. Figure 3. Percentage of patients with positive findings in rhinolaryngoscopy and induced sputum among all of the chronic cough patients. PND: postnasal drip on rhinolaryngoscopy; LPR: laryngopharyngeal reflux on rhinolaryngoscopy. 370
Tuberculosis and Respiratory Diseases Vol. 69. No. 5, Nov. 2010 Table 2. Frequency cross tabulation of related symptoms and objective findings (endoscopic postnasal drip and sputum eosinophilia) Symptom Endoscopic PND Sputum eosinophilia Symptom (-) (+) Total (-) (+) Total (+) 7 22 29 (+) 15 12 27 Dyspnea Dyspnea (-) 37 34 71 (-) 59 11 70 (+) 24 46 70 (+) 16 12 28 Sputum Wheezing (-) 20 10 30 (-) 58 11 69 (+) 10 25 35 (+) 21 13 34 Congestion Congestion (-) 34 31 65 (-) 53 10 63 (+) 13 29 42 (+) 4 5 9 PND sense Belching (-) 31 27 58 (-) 70 18 88 PND: postnasal drip. Figure 4. The comparison of frequency of symptoms according as whether postnasal drip (PND) existed on rhinolaryngoscopy. *p-value <0.05, p-value <0.01. 환자에비하여호흡곤란 (p=0.011), 객담 (p=0.003), 코막힘 (p=0.023), 후비루감각 (p=0.025) 등의증상호소가더많았다 (Figure 4). 그리고비내시경에서후비루를보이는환자의 39% (22/56), 82% (46/56), 45% (35/56), 52% (29/56) 에서호흡곤란, 객담, 코막힘, 후비루감각을각각호소하였다 (Table 2). 후두내시경에서인후두역류소견을보이는환자와그렇지않은환자의증상은유의한차이 Figure 5. The comparison of frequency of symptoms between laryngopharyngeal reflux (LPR) negative and LPR positive patients on rhinolaryngoscopy. PND: postnasal drip. 가없었다 (Figure 5). 객담호산구증가증을보이는환자는그렇지않은환자에비하여호흡곤란 (p=0.003), 쌕쌕거림 (p=0.005), 코막힘 (p=0.013), 구역 (p=0.018) 등의증상호소가더많았다 (Figure 6). 객담호산구증가증을보였던환자의 52% (12/23), 52% (12/23), 57% (13/23), 22% (5/23) 에서호흡곤란, 쌕쌕거림, 코막힘, 구역을각각 371
HK Kim et al: Relation between symptoms and objective findings in chronic cough patients Figure 6. The comparison of frequency of symptoms depending on the existence of sputum eosinophilia. PND: postnasal drip. *p-value <0.05, p-value <0.01. 호소하였다 (Table 2). 고 본연구결과객담, 호흡곤란, 코막힘, 후비루감각등의증상은내시경의후비루소견과연관성이있었고호흡곤란, 쌕쌕거림, 코막힘, 구역등은객담호산구증가증과관련이있었다. 하지만, 내시경의인후두역류소견은모든증상과관련이없는소견임을확인하였다. 성인의만성기침진단에기침의특징및시간과관련된합병증을포함한자세한병력청취는큰도움이안되는것으로알려져있다 8,9. 이러한이유때문에만성기침환자의진단적접근에경험적치료가중요한역할을한다. 하지만경험적치료전에원인에대한정확한평가는만성기침의진단및치료를더수월하게할수있을것이다. 현재까지많은연구가이루어지지는않았지만비후두내시경과객담호산구분석은경험적약물투여전에만성기침의원인에대한평가에도움을준다는긍정적인보고가있다 10. 하지만현재국내의의료기관에서는만성기침환자를대상으로비후두내시경이나객담호산구분석을실제적으로하는곳은적다. 주관적증상과객관적소견의연관성에관한본연구는만성기침환자의객관적인소견을주관적인증상으로추정해보고자하였다. 연구결과대상환자중 56% 에서비내시경에서후비루소 찰 견이관찰되었다. 후비루와관련이있는증상은객담, 호흡곤란, 코막힘, 후비루감각등이었다. 그리고호흡곤란, 객담, 코막힘, 후비루감각각각을호소하는환자의 76% (22/29), 66% (46/70), 71% (25/35), 69% (29/42) 에서후비루가관찰되었다. 그리고내시경에서후비루를보인환자의 82% 가객담을호소하였다 (Table 2). 호흡곤란이후비루를예측하는데유용할가능성이있었고또한호흡곤란을호소하는환자중 97% 의환자가객담을호소하고있었기때문에비내시경에서후비루가빈번하게보일것으로추측해볼수있겠다. 내시경을통한후비루의진단은현재전문가들사이에서도합의된기준이없는상태이다. 본연구에서는비후두내시경에서흔히보이는비인두의분비물에한정하여후비루를정의하였고후비루소견이증상과어떤관련성이있는지확인하고자하였다. 또한후비루의정도를 1+ 4+로나눈기준이따로없었고검사자의주관적인판단으로결정하였다. 내시경소견에서 1+의경우는약간의후인두점막분비물로정상인에서도생리적으로관찰될수있을경우로하였고 2+ 4+를각각경도, 중등도, 고도의후비루의존재로기술하였다. 후두내시경에서보이는인후두역류소견은환자가호소하는모든증상과관계가없었다. 이는증상을통해서인후두역류의소견을예측하기힘들다는것을나타낸다. 인후두역류소견이특정증상을일으키는형태적변화라기보다는기침을포함한다양한증상에의해유발되는이차적인형태변화일가능성을고려할수있겠다. 하지만본연구에서는인후두역류와관련될것으로예측되는증상들을호소하는환자수가적어서이에대한판단은더많은환자를대상으로하는연구를통해서확인될수있을것이다. 외국의연구에따르면내시경을통한인후두역류소견은매우유용한소견으로인후두역류에대한진단및치료후경과관찰에도움을받을수있는것으로알려져있다. 인후두역류의후두내시경소견은비특이적인후두자극및염증에의한변화로점막의비후와발적, 부종등이후두의뒤쪽에서주로관찰된다 (posterior laryngitis) 11. 인후두역류는질병특유의소견이없기때문에 Belafsky 등 4 은후두경소견을 8개의항목으로구분하여점수화하여 (reflux finding score) 인후두역류를평가하고추적관찰을하는데사용하도록하였고, 점수가 7점이상인경우에는 95% 의정확도로인후두역류를진단할수있음을보고하였다. 372
Tuberculosis and Respiratory Diseases Vol. 69. No. 5, Nov. 2010 만성기침환자의약 30% 환자에서 3% 이상의객담호산구증가가관찰된다 12. 본연구에서객담호산구증가증은 23.7% 로국내외다른연구에비해서약간낮은빈도를보였다 6,13. 이는대상환자의기침의기간, 투약력등의차이에의한것으로판단된다. 객담호산구증가와관련된증상은호흡곤란, 쌕쌕거림, 코막힘, 구역등으로각증상의 44% (12/27), 43% (12/28), 38% (13/34), 56% (5/9) 에서객담호산구증가를보였다 (Table 2). 각각의관련증상을통해서객담호산구증가를추정하는정도는약하였다. 이로써각각의관련증상을바탕으로객담호산구증가를추정하는것은내시경적후비루를예측하기보다는어렵다는점을확인할수있었다. 객담호산구증가는만성기침환자를평가하는데중요한소견으로기관지천식이나호산구기관지염 (eosinophilic bronchitis) 등에서관찰된다. 호산구기관지염은만성기침의원인중약 13% 까지차지하는질환으로기관지천식과는달리폐활량검사나기도과민성검사에서는정상소견을보이나객담호산구증가가관찰된다 12,14. 유도객담검사를시행하지않는경우에는호산구기관지염을감별할수없어다수의만성기침환자의진단및치료가적절하지못할수있다. 유도객담검사는이처럼만성기침의원인평가를위해서가치있는검사일뿐만아니라기관지천식이나만성폐쇄성폐질환처럼글루코코르티코이드에반응이있을것으로예상되는환자를구별하는데도움을준다. Brightling 등 12 의연구에따르면기침과객담호산구증가를보이는환자는스테로이드치료에객관적인호전반응을보이고글루코코르티코이드투여와함께객담호산구가감소하는것을확인하였다. 본연구의제한점으로는, 첫째로 3차병원에서수행한후향적연구라는점에서대상군의선택비뚤림이있을수있다. 평균기침유병기간이 59개월로길었던점에서알수있듯이대상자들이 1차나 2차병원진료에도불구하고기침이지속되어 3차병원을방문한환자들로연구결과가모든만성기침환자에해당되지는않을것이다. 본연구가엄밀한의미에서후향적연구이기는하지만만성기침레지스트리형태로체계적으로입력한자료를활용한것이라준전향적연구라할수있다. 둘째로비후두내시경소견을정량화하지못해결과판독에주관성을배제하기어렵다. 하지만검사를한명의알레르기내과전문의가시행해서소견에대한일관성은유지되었을것으로판단된다. 셋째로비후두내시경을경직성내시경으로시행해서비강내부전체의평가와후두부를관찰하는데어려운경우도있었다. 최근에는비강및인후두의구조를관찰하는데굴곡성내시경을이용하는경우가많은데, 검사를받는환자는더편하고, 비강이나인후두부위를좀더자세히관찰할수있는장점이있다 15. 본연구결과인후두역류는환자가호소하는주관적증상과객관적검사소견이부합하는관련성을찾을수없었다. 반면, 후비루나객담호산구증가증은환자가호소하는주관적증상과객관적검사소견이부합하는관련성을확인할수는있었다. 감사의글 This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A040153). 참고문헌 1. Irwin RS, Madison JM. The diagnosis and treatment of cough. N Engl J Med 2000;343:1715-21. 2. Pratter MR. Chronic upper airway cough syndrome secondary to rhinosinus diseases (previously referred to as postnasal drip syndrome): ACCP evidence-based clinical practice guidelines. Chest 2006;129 Suppl 1:63S- 71S. 3. Koufman JA, Aviv JE, Casiano RR, Shaw GY. Laryngopharyngeal reflux: position statement of the committee on speech, voice, and swallowing disorders of the American Academy of Otolaryngology-Head and Neck Surgery. Otolaryngol Head Neck Surg 2002;127:32-5. 4. Belafsky PC, Postma GN, Koufman JA. The validity and reliability of the reflux finding score (RFS). Laryngoscope 2001;111:1313-7. 5. Belafsky PC, Postma GN, Koufman JA. Validity and reliability of the reflux symptom index (RSI). J Voice 2002;16:274-7. 6. Sohn SW, Yang MS, Lee SH, Song WJ, Lee SM, Kwon HS, et al. Evaluation of the causes of chronic cough with sputum eosinophilia. Korean J Asthma Allergy Clin Immunol 2007;27:125-30. 7. Kwon NH, Oh MJ, Min TH, Lee BJ, Choi DC. Causes and clinical features of subacute cough. Chest 2006; 129:1142-7. 8. Mello CJ, Irwin RS, Curley FJ. Predictive values of the 373
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