The Obstructive Lung Disease in Northern Sweden study's (OLIN) overall aim is prevention of obstructive airways diseases; asthma, chronic bronchitis and chronic obstructive pulmonary disease (COPD). The first part of the OLIN study was a cross- sectional study in three phases, which aimed to estimate the prevalence obstructive lung diseases and to collect data on possible determinants of diseases. This thesis is based on the first part of the OLIN study, and on a postal survey mainly performed in order to evaluate the external validity of the first part of the project Aims: * To assess the prevalences of asthma, chronic bronchitis and respiratory symptoms in adults. * To compare the influence of various diagnostic criteria on prevalence. * To identify subjects with obstructive lung diseases, in particular asthma, for case-referent and prospective longitudinal studies. * To examine whether the trend towards an increase in the prevalence of asthma persists. * Study factors that may influence the development of obstructive lung diseases; age, gender, smoking habit, occupation, socio-economic group, population density and area of domicile. The first part of the OLIN study consisted of three phases. A postal questionnaire regarding respiratory symptoms and diseases, smoking habit and profession was sent to all subjects aged 35-36 y, 50-51 y and 65-66 y (n=6,610) living in eight representative areas of Sweden's northernmost province; 86% completed the questionnaire. Those reporting symptoms suspicious of asthma or chronic bronchitis (n=l,340), together with a stratified sample (n=315) of those not suspected of having the diseases according to the postal questionnaire, were invited to structured interviews and lung function tests. The prevalence of asthma, 5- 6% according to both the postal questionnaire and to the structured interview, prompted a validity study, which included bronchial provocation tests. While the prevalence remained unchanged, the validity study better identified the subjects with asthma and chronic bronchitis, thus improving the representativeness of the subjects with the diseases. In 1992, the study base was expanded by a postal questionnaire study which included 20/489 subjects 20-69 y in order to assess whether the prevalence had changed, to create possibilities to estimate the incidence, and to be better able to detect determinants of diseases. The results show that the prevalence of asthma in adults in 1992 was 7-8% according to postal questionnaire and was considerably higher, approximately 10%, in young adults. Further, the prevalence of asthma in 1986-1987 in subjects aged 35-36 y, 50-51 y and 65-66 y was 5% by using a combination of epidemiological and clinical methods. Various operational criteria yielded a prevalence of 4-7%. Between 1986 and 1992 the prevalence of asthma in these age groups increased with 1% according to the postal questionnaire. Chronic bronchitis in subjects aged 35-36 y was 3% in 1986-1987. The prevalence of chronic bronchitis increased with age, particularly in men. The mean prevalence in the three age groups 35-36 y, 50-51 y and 65-66 y was 12% in men and 8% in women. Chronic bronchitis was strongly associated with smoking, age and a family history of obstructive airways disease. Regarding socioeconomic group chronic bronchitis was related to manual workers in industry and to self- employed other than professionals, and it was particularly common in miners and in those employed in agriculture. The strongest risk factor for asthma was a family history of asthma, and asthma was more common in manual workers in service, in non-manual assistant employees as well as in farmers. The results also indicate the presence of an urban factor in asthma in northern Sweden, in spite of the fact that respiratory symptoms in general tended to be more common in the colder interior of the province compared with the coastal area. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1993, härtill 7 uppsatser</p> / digitalisering@umu

Background: The clinical and pathological presentation of COPD is heterogeneous. ‘Chronic bronchitis’ is a phenotype of COPD, which is a clinical diagnosis of a productive cough of ≥ 3 months for ≥ 2 consecutive years. Chronic bronchitis is associated with worse lung function, frequent exacerbations, recurrent hospitalisations and premature death in patients with COPD. Chronic bronchitis sufferers can be further subphenotyped into those who produce sputum during exacerbation or during winter months only and those who are ‘persistent sputum producers,’ who experience mucous hypersecretion throughout the year. An improved understanding of persistent sputum producers is the object of this thesis. Aims: 1) To compare the clinical characteristics and airway inflammatory biomarker profile of COPD persistent sputum producers to that of COPD sputum non-producers 2) To investigate the short term repeatability of sputum parameters in COPD persistent sputum producers 3) To study the expression and relationship of mucins, hypoxia inducible factor (HIF-1α) and carbonic anhydrase IX (CAIX) in COPD persistent sputum producers. Methods: 1) Lung physiology, health status, sputum inflammatory biomarkers and sputum culture results were compared between COPD persistent sputum producers and sputum non-producers 2) Repeatability of spontaneous and induced sputum parameters at 8 weeks was assessed in COPD persistent sputum producers 3) Immunohistochemistry was performed on bronchial biopsies of COPD persistent sputum producers and control groups (COPD sputum non-producers, smokers with normal lung function and lifelong healthy non-smokers with normal lung function) to study the expression of MUC5AC, MUC5B, HIF-1α and CAIX 4) The association between HIF-1α and MUC5B expression was investigated in vitro. Results and Conclusions: The findings suggest that 1) COPD persistent sputum producers have clinically more severe disease, increased airway inflammation, increased impact on health status, increased rate of bacterial colonization and higher number of exacerbations compared to COPD sputum non-producers 2) Induced sputum is repeatable over short term in COPD persistent sputum producers 3) Expression of MUC5B, HIF-1α and CAIX is increased in COPD persistent sputum producers compared to COPD sputum non-producers, smokers with normal lung function and healthy non-smokers 4) HIF-1α can potentially cause increased MUC5B expression. This work reveals potential targets for the development of novel therapies to limit mucous hypersecretion in COPD.

El objetivo del estudio era identificar las exposiciones ocupacionales relacionadas con asma en empleadas de limpieza doméstica. Un estudio poblacional transversal realizado en 4,521 mujeres mostró que las empleadas del hogar tenían un mayor riesgo de asma y bronquitis crónica que las mujeres que nunca habían trabajado en limpieza. Posteriormente, se realizo un estudio caso-control en empleadas del hogar que incluia 40 casos de asma y/o bronquitis crónica y 155 controles. Los casos estaban expuestos más frecuentemente a lejía y a fregar los platos y habían sufrido más accidentes de inhalación con productos de limpieza. Finalmente, en un estudio de panel en 43 empleadas del hogar con problemas respiratorios, se observó empeoramiento de los síntomas de las vías respiratorias inferiores los días de trabajo y los días expuestos a lejía, desengrasantes y/o ambientadores. Se concluye que las empleadas del hogar tienen un aumento en el riesgo de asma y posiblemente bronquitis crónica y que dicho riesgo está relacionado principalmente con exposiciones irritantes. / We aimed to investigate the relationship between occupational exposures and asthma in women employed in domestic cleaning. A population-based cross-sectional study among 4,521 women showed that domestic cleaners had an increased risk of asthma and chronic bronchitis symptoms as compared with those never employed in cleaning. Subsequently, a case-control study among domestic cleaning women was conducted including 40 cases of asthma and/or chronic bronchitis and 155 controls. Cases were more frequently exposed to bleach and washing dishes and had experienced more inhalation accidents involving cleaning products than controls. Finally, a panel study among 43 domestic cleaning women with respiratory symptoms showed aggravation of lower respiratory symptoms on working days and on days with exposure to bleach, degreasers and/or air-fresheners. In conclusion, women employed in domestic cleaning are at an increased risk of asthma and possibly chronic bronchitis, this risk being predominantly related to irritant exposures.

Σκοπός της παρούσας μελέτης ήταν να αξιολογηθεί το αγγειομετατρεπτικό ένζυμο στον ορό των ασθενών με πνευμονία, ως διαγνωστικός ή/και προγνωστικός δείκτης της νόσου και γενικά να μελετηθούν οι διάφοροι προγνωστικοί παράγοντες στις λοιμώξεις του κατώτερου αναπνευστικού συστήματος. / Objective: The aim of this study was to determine prognostic factors of outcome in patients with lower respiratory tract infections (LRTIs). LRTIs are an heterogeneous group of disorders, including acute bronchitis, pneumonia, superinfection of chronic bronchitis and flu. The recent publications of several prognostic factors of outcome address specific conditions such as pneumonia or bronchitis, while general practitioners cannot usually differentiate between these conditions in current practice. Methodology: A total of 616 patients with LRTIs were retrospectively reviewed with regard to epidemiological, clinical, laboratory and radiographic data. The prognostic analysis included an univariate as well as a multivariate approach, in order to identify parameters associated with death. Results: The parameters found to be significantly different between survivors and non survivors in the univariate analysis, were respiratory rate (p<0,01), oxygen partial pressure (PaO2) (p<0,001), heart rate (p<0,0003), systolic and diastolic blood pressure (p<0,047 and (p<0,022, respectively), platelet count (p<0,045), urea (p<0,002), creatinine Objective: The aim of this study was to determine prognostic factors of outcome in patients with lower respiratory tract infections (LRTIs). LRTIs are an heterogeneous group of disorders, including acute bronchitis, pneumonia, superinfection of chronic bronchitis and flu. The recent publications of several prognostic factors of outcome address specific conditions such as pneumonia or bronchitis, while general practitioners cannot usually differentiate between these conditions in current practice. Methodology: A total of 616 patients with LRTIs were retrospectively reviewed with regard to epidemiological, clinical, laboratory and radiographic data. The prognostic analysis included an univariate as well as a multivariate approach, in order to identify parameters associated with death. Results: The parameters found to be significantly different between survivors and non survivors in the univariate analysis, were respiratory rate (p<0,01), oxygen partial pressure (PaO2) (p<0,001), heart rate (p<0,0003), systolic and diastolic blood pressure (p<0,047 and (p<0,022, respectively), platelet count (p<0,045), urea (p<0,002), creatinine (p<0,002), previous admission in the hospital the last year (p<0,033), and cavitations in chest radiograph (p<0,047). In multivariate analysis, the only statistically significant risk factors were PaO2 (odds ratio (OR) =0,8574; 95% confidence interval (CI) 0,7499-0,9802 in non survivors compared to survivors) and heart rate (OR=1,063; 95% CI 1,0052-1,1241 in non survivors compared to survivors). Conclusions: LRTIs remain a widespread problem and have a significant impact on primary healthcare resources. The great variability seen in rates of hospital admission and lengths of stay in part reflects uncertainty among physicians in assessing the severity of the illness. According to our data, PaO2 and heart rate, were most closely associated with death in patients with LRTIs. These predictor variables are all explicitly defined and can be readily assessed at the time of patient presentation.

Aim. To assess associations between occupational air pollution and respiratory health, especially in miners. Background. Indications of associations between occupational exposure or social economic status and respiratory health have been found in several population-based studies. However, there have been few longitudinal studies of the putative correlations, the effects of environmental and genetic factors have seldom been simultaneously studied, and studies of miners have generated conflicting results. Material and methods. Population-based Obstructive Lung Disease in Northern Sweden (OLIN) cohorts surveyed in 1986, 1992 and 1996, and two industry-based materials, were used in cross-sectional and longitudinal studies. Inflammatory markers were compared in sputa from miners after a vacation of at least four weeks, after repeated occupational exposures for at least three months, and controls. The mortality from silicosis was studied in 7729 miners with at least 1 year of exposure. Multivariate analyses were used to adjust for confounders. Results. Up to about 30-40% (etiologic fraction) of incident symptoms in persons both with and without a family history of asthma (FHA) could be explained by exposure to occupational air pollution. Low socio-economic status (SES) was associated with impaired respiratory health. Population attributable risks for most examined disorders were about 10%. Current and ex-miners had increased prevalence of recurrent wheeze, longstanding cough, physician-diagnosed chronic bronchitis, and a trend for increased sputum production. For physician-diagnosed chronic bronchitis a multiplicative interaction was found between exposure and smoking habits. Ex-miners that had been exposed for on average 13 years and whose exposure had ceased 16 years before the study had an increased prevalence of physician-diagnosed chronic bronchitis and chronic productive cough and a trend to increased use of asthma medicines. Miners exposed underground for 18 years, on average, to diesel exhaust (with 0.28 mg/m3 nitrogen dioxide and 27 μg/m3 elemental carbon on average, EC) and particles (3.2 mg/m3 inhalable dust on average) had signs of higher inflammatory activity in their airways, i.e. significantly higher frequencies of macrophages, neutrophils, and total cells compared with referents. The activity in miners was similar after a vacation of at least four weeks and after repeated exposures for three months. There were 58 deaths from silicosis (underlying and contributing cause of death) and a clear dose-response relationship. The data indicated an increased risk of severe silicosis after long-term exposure to 0.1 mg/m3 respirable quartz, the current maximum allowable concentration (MAC) in Sweden and many other countries. Conclusion. Occupational exposure to dust, gases, and fumes impaired respiratory health, accounting for up to 30-40% of some respiratory symptoms in the general population. Low socio-economic status was associated with impaired respiratory health. The complex profiles of dust and diesel exhaust substances found in mines may cause inflammatory reactions in their lungs and persistent respiratory symptoms in occupationally exposed miners. Long-term exposure to quartz at the present MAC level may cause severe silicosis.

Chronic respiratory diseases such as asthma and chronic bronchitis have significantly increased in prevalence in Africa over the past 10 years. Recent studies have demonstrated that exposure to air pollution may be associated with an increased risk of chronic respiratory diseases. However, such studies have predominantly been conducted in western societies or often used urbanicity as a proxy for exposure to air pollution. Therefore, we evaluated the association between PM2.5 exposure and asthma/chronic bronchitis in Senegal. A cross-sectional study was conducted for the time period of 3 October 2010 to 28 April 2011 using annual concentrations of PM2.5 measured via multiple satellite instruments, and asthma/chronic bronchitis, which was self-reported at baseline via a health survey questionnaire. We used mixed model logistic regression to evaluate the relationship between PM2.5 exposure and asthma/chronic bronchitis risk while adjusting for lifestyle factors, location, and other air pollutants. Sex was evaluated as an effect modifier. The adjusted association between PM2.5 and asthma/chronic bronchitis was 1.03 (95%CI: 0.99 – 1.06). In males the adjusted odds ratio was 1.09 (95%CI: 1.03-1.15), compared to females (aOR 1.01 (95%CI: 0.97 – 1.05). Our results suggest that increasing levels of exposure to PM2.5 puts individuals at a higher risk for chronic respiratory diseases, especially men. These findings have significant policy implications and should be built upon in future research.

Chronic obstructive pulmonary disease is the fourth largest cause of death worldwide and the prevalence is predicted to increase even further to make it the third largest cause of death by 2020. The main cause of the disease is exposure to tobacco smoke. COPD is a complex disease and there is a strong need of better understanding of the pathogenetic mechanisms in order to come up with novel therapeutic interventions and preventive strategies. The golden standard to image the lungs today is to use computed tomography (CT) which is an imaging modality that involves ionizing radiation and could thus harm the patient, especially with repeated exposure. New techniques in the image acquisition of magnetic resonance imaging (MRI), an imaging modality that does not involve ionizing radiation, has emerged that allows for lung imaging. The work included segmentation of the lungs, image registration and partitioning of the lungs inorder to perform regional analysis. The results indicate that the mean value of the T1-parameter in the left and right lung is not affected to the same degree, where the left lung showed a greater decrease. The results also showed that the anterior parts of the lungs are not showing any statistically significant changes but the changes were instead seen in the center and posterior parts. Both lungs also showed results that indicate that the mean T1-value is recovered at the end of the longitudinal study, a phenomenon that couldn’t be explained and further studies have to be performed.

Abstract Although smoking in adolescents and young adults has been declining in the 21st century in Finland, about 17% of 18-year-olds still smoke on a daily basis. Young adults are in fact one of the age groups that are most likely to smoke in several countries. Nevertheless, a large proportion of them are known to want to quit smoking. Relatively little is known about the smoking habits of young adults. There are no evidence-based guidelines for smoking cessation in this age group. In many cases, they have been included within studies of adolescents or older adults without any separate analysis. Consequently, smoking cessation interventions demonstrated to be effective in middle-aged smokers are often adapted for young adults even though their culture, somatic features and smoking habits in many ways are different from those of middle-aged people. This study focused on 18–26-year-olds in northern parts of Finland. Specific aims were 1) to describe their smoking habits, 2) to compare health and lifestyle in tobacco users and non-tobacco users, 3) to study their nicotine dependence and motivation to quit smoking, and 4) to examine the use and effectiveness of smoking cessation pharmacotherapy in this age group. A total of 1163 male military recruits from northern parts of Finland filled in the study questionnaire. The survey study revealed that young adult males in northern parts of the country used tobacco products relatively often. Their smoking was associated with lower education, higher body mass index, inactivity in sports and impaired physical fitness. In addition, a great part of young smokers displayed symptoms of chronic bronchitis. Although most daily smokers were clearly dependent on nicotine and had previously tried to quit smoking, only 47% of the quitters had utilized any pharmacological aids in their attempts. Snus use seemed to be related to more severe nicotine dependence in smokers. The prospective study consisted of 314 voluntary young adult daily smokers who were motivated to quit smoking. The study was a randomised, placebo-controlled clinical trial, and the results indicated that varenicline might be more effective than nicotine patches in smoking cessation of young adult heavy smokers, at least in short term. Abstinence rates during the follow-up were similar when the nicotine patch and placebo patch were compared in young adult light smokers. / Tiivistelmä Suomessa nuorten keskuudessa tupakointi on ollut 2000-luvun aikana laskusuuntainen. Kuitenkin arviolta n. 17 % 18-vuotiaista tupakoi edelleen päivittäin. Nuoret aikuiset ovatkin useissa maissa yksi eniten tupakoivia ikäryhmiä. Silti suuren osan tupakoivista nuorista aikuisista on todettu olevan halukkaita llopettamaan tupakoinnin. Nuorten aikuisten tupakointia on tutkittu verrattain vähän. Heille suunnattuja tieteelliseen näyttöön perustuvia hoitomuotoja tupakoinnin lopettamiseen ei ole. He ovat usein osana teini-ikäisten tai vaihtoehtoisesti vanhempien aikuisten ryhmää tupakointiin liittyvissä tutkimuksissa, eikä heitä yleensä ole analysoitu erikseen. Usein heitä hoidetaankin keski-ikäisiltä aikuisilta saadun tutkimusnäytön pohjalta. Kuitenkin nuorten kulttuuri, biologinen pohja ja tupakointitavat eroavat merkittävästi vanhemmista tupakoitsijoista. Tämä työ on keskittynyt tutkimaan 18–26-vuotiaita nuoria aikuisia Pohjois-Suomessa. Sen tavoitteina on ollut 1) kuvata heidän tupakointitottumuksiaan, 2) selvittää tupakoinnin yhteyttä terveyteen ja elämäntapaan, 3) tutkia heidän nikotiiniriippuvuuttaan sekä motivaatiota lopettaa tupakointi, sekä 4) selvittää tupakkavieroituslääkkeiden käyttöä ja niiden tehoa tässä ikäryhmässä. Terveystottumuskyselyymme vastasi 1163 Pohjois-Suomen varusmiestä. Selvisi, että varusmiehet käyttivät tupakkatuotteita Pohjois-Suomessa valtakunnallisia arvioita enemmän. Tupakoinnin todettiin liittyvän varusmiehillä alempaan koulutustasoon, suurentuneeseen painoindeksiin, vähäisempään fyysiseen aktiivisuuteen ja huonompaan aerobiseen suorituskykyyn. Lisäksi tupakoivilla varusmiehillä kroonisen bronkiitin oireet olivat yleisiä. Vaikka valtaosa heistä oli selvästi nikotiiniriippuvaisia ja oli yrittänyt lopettaa tupakointinsa, vain 47% lopetusta yrittäneistä oli kokeillut tupakkavieroituslääkettä. Nuuskan käyttö vaikutti liittyvän vahvempaan nikotiiniriippuvuuteen tupakoitsijoilla. Prospektiiviseen, satunnaistettuun ja lumekontrolloituun kliiniseen kokeeseen osallistui 314 vapaaehtoista päivittäin tupakoivaa nuorta aikuista, jotka olivat halukkaita tupakoinnin lopetukseen. Tulokset viittasivat siihen, että varenikliini saattaa olla nikotiinilaastaria tehokkaampi tupakoinnista vieroituksessa vahvasti nikotiiniriippuvaisilla nuorilla aikuisilla ainakin lyhyellä aikavälillä. Kevyemmin tupakasta riippuvaisilla nikotiinilaastari ei ollut lumelaastaria tehokkaampi.

Mais de 60% dos pacientes com Doença Pulmonar Obstrutiva Crônica (DPOC) podem apresentar hiper-responsividade brônquica. Entretanto, não se sabe se, além das vias aéreas, o tecido pulmonar periférico também apresenta uma resposta exagerada a um agonista na DPOC. No presente estudo foi investigado o comportamento mecânico in vitro e as alterações estruturais e inflamatórias do tecido pulmonar periférico de 10 pacientes com DPOC comparados com 10 controles não fumantes. Foram realizadas medidas de resistência (R) e elastância (E) de fatias pulmonares em situação basal e após desafio com Acetilcolina. Também foram analisados no tecido alveolar as densidades de neutrófilos, eosinófilos, macrófagos, mastócitos e linfócitos CD8+ e CD4+, além do conteúdo de células positivas para -actina de músculo liso, fibras elásticas e colágenas. Os valores de R após o tratamento com Acetilcolina (RACh) e a porcentagem de aumento de resistência (%R) foram significativamente maiores no grupo DPOC comparado ao grupo controle (p0,03). O grupo DPOC também apresentou densidade de macrófagos (p=0,04) e linfócitos CD8+ (p=0,017) significativamente maior e conteúdo de fibras elásticas significativamente menor (p=0,003) comparado ao grupo controle. Foi observada uma correlação positiva significativa entre a %R e a densidade de eosinófilos e linfócitos CD8+ (r=0,608, p=0,002; e r=0,581, p=0,001, respectivamente), e também uma correlação negativa significativa entre a %R e a relação VEF1/ CVF (r=-0,451, p<0,05). Concluímos que a resposta colinérgica de fatias de parênquima pulmonar está aumentada em pacientes com doença pulmonar obstrutiva crônica e parece estar relacionada tanto à densidade de eosinófilos e de linfócitos CD8+ no tecido alveolar quanto ao grau de obstrução determinado pela prova de função pulmonar. / Up to 60% of COPD patients can present airway hyperresponsiveness. However, it is not known whether the peripheral lung tissue also presents an exaggerated response to agonists in COPD. In this study we investigated the in vitro mechanical behavior and structural and inflammatory changes of peripheral lung tissue of 10 COPD patients and compared to 10 non-smoking controls. We measured resistance (R) and elastance (E) of lung strips at baseline and after acetylcholine (ACh) challenge. We further assessed the alveolar tissue density of neutrophils, eosinophils, macrophages, mast cells and CD8+ and CD4+ cells, and the content of -smooth muscle actin+ cells, elastic fibers and collagen fibers. Values of R after ACh treatment (RACh) and percent increase of tissue resistance (%R) were significantly higher in COPD group compared to controls (p0.03). There was a significantly higher density of macrophages (p=0.04) and CD8+ cells (p=0.017) and a lower elastic fiber content (p=0.003) in COPD group compared to controls. We observed a significant positive correlation between %R and eosinophil and CD8+ cells density (r=0.608, p=0.002; and r=0.581, p=0.001, respectively), and also a negative correlation between %R and FEV1/FVC (r=-0.451, p<0.05). We conclude that the cholinergic responsiveness of parenchymal lung strips is increased in COPD patients and seems to be related to alveolar tissue eosinophilic and CD8 lymphocytic inflammation and also to the degree of airway obstruction at pulmonary function test.

Mais de 60% dos pacientes com Doença Pulmonar Obstrutiva Crônica (DPOC) podem apresentar hiper-responsividade brônquica. Entretanto, não se sabe se, além das vias aéreas, o tecido pulmonar periférico também apresenta uma resposta exagerada a um agonista na DPOC. No presente estudo foi investigado o comportamento mecânico in vitro e as alterações estruturais e inflamatórias do tecido pulmonar periférico de 10 pacientes com DPOC comparados com 10 controles não fumantes. Foram realizadas medidas de resistência (R) e elastância (E) de fatias pulmonares em situação basal e após desafio com Acetilcolina. Também foram analisados no tecido alveolar as densidades de neutrófilos, eosinófilos, macrófagos, mastócitos e linfócitos CD8+ e CD4+, além do conteúdo de células positivas para -actina de músculo liso, fibras elásticas e colágenas. Os valores de R após o tratamento com Acetilcolina (RACh) e a porcentagem de aumento de resistência (%R) foram significativamente maiores no grupo DPOC comparado ao grupo controle (p0,03). O grupo DPOC também apresentou densidade de macrófagos (p=0,04) e linfócitos CD8+ (p=0,017) significativamente maior e conteúdo de fibras elásticas significativamente menor (p=0,003) comparado ao grupo controle. Foi observada uma correlação positiva significativa entre a %R e a densidade de eosinófilos e linfócitos CD8+ (r=0,608, p=0,002; e r=0,581, p=0,001, respectivamente), e também uma correlação negativa significativa entre a %R e a relação VEF1/ CVF (r=-0,451, p<0,05). Concluímos que a resposta colinérgica de fatias de parênquima pulmonar está aumentada em pacientes com doença pulmonar obstrutiva crônica e parece estar relacionada tanto à densidade de eosinófilos e de linfócitos CD8+ no tecido alveolar quanto ao grau de obstrução determinado pela prova de função pulmonar. / Up to 60% of COPD patients can present airway hyperresponsiveness. However, it is not known whether the peripheral lung tissue also presents an exaggerated response to agonists in COPD. In this study we investigated the in vitro mechanical behavior and structural and inflammatory changes of peripheral lung tissue of 10 COPD patients and compared to 10 non-smoking controls. We measured resistance (R) and elastance (E) of lung strips at baseline and after acetylcholine (ACh) challenge. We further assessed the alveolar tissue density of neutrophils, eosinophils, macrophages, mast cells and CD8+ and CD4+ cells, and the content of -smooth muscle actin+ cells, elastic fibers and collagen fibers. Values of R after ACh treatment (RACh) and percent increase of tissue resistance (%R) were significantly higher in COPD group compared to controls (p0.03). There was a significantly higher density of macrophages (p=0.04) and CD8+ cells (p=0.017) and a lower elastic fiber content (p=0.003) in COPD group compared to controls. We observed a significant positive correlation between %R and eosinophil and CD8+ cells density (r=0.608, p=0.002; and r=0.581, p=0.001, respectively), and also a negative correlation between %R and FEV1/FVC (r=-0.451, p<0.05). We conclude that the cholinergic responsiveness of parenchymal lung strips is increased in COPD patients and seems to be related to alveolar tissue eosinophilic and CD8 lymphocytic inflammation and also to the degree of airway obstruction at pulmonary function test.