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IntroductionThe value of chest auscultation would be enhanced by the use of a standardised terminology. To that end, the recommended English terminology must be transferred to a language other than English (LOTE) without distortion.ObjectiveTo examine the transfer to Hebrew—taken as a model of LOTE—of the recommended terminology in English.Design/settingCross-sectional study; university-based hospital.Participants143 caregivers, including 31 staff physicians, 65 residents and 47 medical students.MethodsObservers provided uninstructed descriptions in Hebrew and English of audio recordings of five common sounds, namely, normal breath sound (NBS), wheezes, crackles, stridor and pleural friction rub (PFR).Outcomes(a) Rates of correct/incorrect classification; (b) correspondence between Hebrew and recommended English terms; c) language and auscultation skills, assessed by crossing the responses in the two languages with each other and with the classification of the audio recordings validated by computer analysis.ResultsRange (%) of correct rating was as follows: NBS=11.3–20, wheezes=79.7–87.2, crackles=58.6–69.8, stridor=67.4–96.3 and PFR=2.7–28.6. Of 60 Hebrew terms, 11 were correct, and 5 matched the recommended English terms. Many Hebrew terms were adaptations or transliterations of inadequate English terms. Of 687 evaluations, good dual-language and single-language skills were found in 586 (85.3%) and 41 (6%), respectively. However, in 325 (47.3%) evaluations, good language skills were associated with poor auscultation skills.ConclusionPoor auscultation skills surpassed poor language skills as a factor hampering the transfer to Hebrew (LOTE) of the recommended English terminology. Improved education in auscultation emerged as the main factor to promote the use of standardised lung sound terminology. Using our data, a strategy was devised to encourage the use of standardised terminology in non-native English-speaking countries.

Background Different case finding approaches have been used to identify early COPD. The objective of this study was to assess the feasibility and the yield of opportunistic early COPD case finding in visitors to a large medical centre. Patients and Methods From May 2014 to June 2017, we consecutively recruited adults aged ≥ 18 years visiting the Shaare Zedek Medical Center, in Jerusalem. Our 3-step intervention included: a) pre-screening for symptoms with the 5-item “Could it be COPD?” questionnaire (score= 0–5 pts); b) pre-BD spirometry; and c) referral to a caregiver. Airflow obstruction was defined by a FEV1/FVC < 0.7. Spirometry results were used as an incentive to promote smoking cessation and quit rates were verified by phone survey 3 months after the intervention. Results A total of 1001 subjects (956 smokers; 45 ex-smokers) were recruited. Mean (SD) age was 48.3 years (13.5). Airflow obstruction was detected in 180 (18%) subjects of whom 142 (78.9%) were unaware of it, including 27 subjects with severe (50% ≥ FEV1 ≤ 30% predicted) (n=25) or very severe (FEV1 < 30% predicted) (n=2) obstruction. Multiple logistic regression analysis found that age, BMI, cigarette smoking (p.y.) and a “Could it be COPD?” questionnaire score ≥ 3 points correctly classified 83.3% of cases of airflow obstruction. At follow-up, 54.5% of participants reported smoking as usual, 30.9% reduced smoking [mean (SD) = 10.1 ± 7.8 cigarettes/day], 7.4% increased smoking [mean (SD) = 9.2 ± 6.3 cigarettes/day] and 7.2% claimed smoking cessation. Among obstructed subjects, 38.7% had visited a physician because of COPD, while 20.7% were taking a new respiratory medication. Conclusion Early COPD case finding was feasible and effective in identifying undiagnosed airflow obstruction among visitors to a medical centre. Smoking cessation counselling based on spirometry promoted a small but clinically meaningful cessation rate., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/mIHcx3D4D9k

The methacholine challenge test (MCT) is primarily indicated to help determine if current respiratory symptoms may be due to asthma or not (1,2). A positive test is generally defined as the provocative concentration (or dose) of methacholine causing a 20% fall in forced expiratory volume in one second (PC20FEV1) without consideration of the symptoms that may occur during the test, such as dyspnoea, cough, chest tightness and wheezing (2).

International audience; Purpose : Conventionally, symptoms occurring during the methacholine test are not taken into account when interpreting the test results. We examined whether the evaluation of methacholine-induced symptoms (MIS) added to the test interpretation based on the PC20FEV1 by assessing their prevalence, their similarity with symptoms justifying referral and their relationship with airway responsiveness.Methods : Eighty-two patients with suspected asthma completed a questionnaire of symptoms and underwent bronchial challenge with methacholine. Based on MIS and airway responsiveness (responders = PC20FEV1

Background: Initiating varenicline use 4 weeks before the target quit date (TQD) reduces smoking in the run-in phase and increases end-treatment cessation rates; however, the lack of a smoke intake plateau suggests longer preloading periods are required. This study assessed whether varenicline preloading for 6 weeks reduced pre-quit smoke intake and enhanced 6-month abstinence outcomes compared with the standard 1-week preloading. Methods: In this randomised single-centre controlled trial, (ClinicalTrials.gov identifier: NCT02634281), conducted between February 2016 and July 2018 in Israel, daily smokers (n = 242) aged ≥ 18 years were randomly assigned (1:1) to receive varenicline preloading for 6 weeks (n = 121) or a placebo for 5 weeks followed by varenicline for 1 week (n = 121) before the TQD. Participants and researchers were masked to both group assignment and treatment allocation. Both groups received standard 12-week post-TQD varenicline treatment. The primary outcome was the 24-week biochemically verified continuous abstinence rate (CAR) from weeks 6 (TQD)–30. Secondary outcomes included the 23-week CAR from 1-week post-TQD (week 7) to week 30, and the 7-day point-prevalence (PP) abstinence at week 30. Other measures included pre- and post-quit rewards, smoking urges, nausea, aversion, and markers of cigarette consumption. Findings: By intention-to-treat, the 24-week CAR, weeks 6–30 with extended preloading was significantly higher than with standard preloading (23·1% vs. 4·1%; risk reduction [RR]: -0·19 [95% confidence interval [CI]:-0·10—0·24]; p < 0·001). Extended preloading also showed better secondary outcomes. Extended preloading significantly decreased pre-quit rewards, urges, and smoke intake, including unsolicited smoking abstinence. Post-quit urges remained remarkably lower with extended preloading. Participants receiving extended preloading reported more nausea at week 4 (39.6% vs 11.5%) and abnormal dreams at week 6 (7.7% vs. 0%). Participants receiving standard preloading reported more constipation at week 7 (7.6% vs. 0%) and dizziness at weeks 7 (12.1% vs. 2.5%) and 12 (10.7% vs 1.4%). Interpretation: Extended preloading reduced ad lib smoking, enhanced cessation rates at 3 and 6 months, and decreased pre- and post-quit rewards and smoking drive in a pattern compatible with a reinforcement-reduction mechanism. These data substantiate extending the standard pre-treatment period, and suggest that targeting pre-quit smoking sensations should be a treatment priority, although confirmatory evidence is needed from larger clinical trials. Funding: This study was funded by a 2013 Global Research Award for Nicotine Dependence (GRAND) supported by Pfizer, Inc. (#WI182915). Keywords: Smoking cessation, Smoking reduction, Varenicline, Extended preloading

Background: Many studies have described asthma-COPD overlap (ACO) among patients diagnosed with asthma or chronic obstructive pulmonary disease (COPD), but less so in broad populations of patients with chronic airway obstruction. Objective: This study aimed to (i) examine the prevalence of ACO, asthma, and COPD phenotypes among subjects referred for pulmonary function testing (PFT), who had airway obstruction in spirometry (forced expiratory volume in 1 s [FEV1]/forced vital capacity [FVC] Methods: Cross-sectional study of patients who were referred for PFT at the Rokach Institute, in Jerusalem. Working definitions were as follows: (a) COPD: post-bronchodilator (BD) FEV1/FVC 1 or FVC of 12% and 200 mL; and (c) ACO: the combination of the 2. Demographics, smoking habits, episodes of exacerbation, health-related quality of life (HRQL), and respiratory medication utilization were analyzed. Results: Of 3,669 referrals from January 1 to April 30, 2017, 1,220 had airway obstruction of which 215 were included. Of these, 82 (38.1%) had ACO, 49 (22.8%) asthma, and 84 (39.1%) COPD. ACO subjects tended to (a) be predominantly female; (b) be older than asthmatics, (c) be smokers; (d) have worse HRQL in the activity domain; and (d) have more exacerbations. Treatment of ACO and COPD patients differed from that of asthmatics, but not from each other, in the proportion of subjects on maintenance treatment, use of LABA, LAMA, and ICS, alone or in combination, and in the number of inhaler devices used by patients. Conclusion: ACO represented >1/3 of patients referred for PFT. Despite a clearly identifiable phenotype, ACO patients received treatment similar to COPD patients, suggesting poor ACO identification. Our data emphasize the need to raise the awareness of ACO among clinicians, in order to guide better recognition and appropriate treatment in individual patients.

Background: In smokers receiving varenicline cessation treatment, increasing the pre-quit period by 3 weeks reduces smoking intake prior to quit attempts and increases cessation rates; however, the lack of an intake plateau suggests longer preload periods are required. We assessed whether varenicline preloading for 6 weeks reduces pre-quit smoke intake and enhances 6-month abstinence outcomes compared with the standard 1-week preloading. Methods: This randomised controlled trial was conducted between February 2016 and July 2018 in Israel. Everyday smokers (n = 242) aged ≥ 18 years were randomly assigned (1:1) to receive extended varenicline preloading for 6 weeks (n = 121) or a placebo for 5 weeks followed by varenicline for 1 week (n = 121) before the target quit date (TQD). Both groups received standard 12-week post-TQD varenicline treatment. Participants and researchers were masked to treatment allocation. Primary outcomes were the 24-week biochemically-verified continuous abstinence rate (CAR) (weeks 6-30) and the 12-week CAR (weeks 6-18). Other measures included pre- and post-quit rewards, smoking urges, nausea, aversion, and markers of cigarette consumption. Analysis involved intention-to-treat. Findings: The 12-week CAR was 24·8% for extended preloading vs. 7·4% for standard preloading (odds ratio [OR], 4·10 [95% confidence interval [CI]: 1·85-9·08]; p < 0·001). The 24-week CAR was 23·1% for extended preloading vs. 4.1% for standard preloading (OR, 6·98 [95% CI: 2·60-18·80]; p < 0·001). Extended preloading significantly decreased pre-quit rewards and urges; nausea increased along with decreased smoke intake, including unsolicited smoking abstinence. In the post-quit period, after beginning the standard varenicline treatment, between-group differences in rewards and nausea subsided; smoking urges remained remarkably lower in the extended preloading group. Extended preloading was safe and well accepted. Interpretation: Extended preloading generated a marked reduction in ad lib smoking, enhanced cessation rates at 3 and 6 months, and increased abstinence rates by promoting a reinforcement-reduction mechanism unnoticed with the standard dosing regimen. Our data substantiate extending the standard pre-treatment period and suggest that targeting pre-quit smoking sensations should be a priority in smoking cessation treatments. Trial Registration: ClinicalTrials.gov (Identifier: NCT02634281). Funding Statement: This study was funded by a 2013 Global Research Award for Nicotine Dependence (GRAND) supported by Pfizer, Inc (#WI182915). Editorial support in the form of editing, proofing and formatting the text and preparing the manuscript for submission was provided by Elsevier Editing Services and funded by the Pulmonary Institute of Shaare Zedek Medical Center. Declaration of Interests: The authors state: "None to declare." Ethics Approval Statement: The study was conducted in compliance with the recommendations guiding physicians in biomedical research involving humans adopted by the 18th World Medical Assembly, Helsinki, Finland, 1964 and later revisions. The “Helsinki Committee” of the SZMC approved all study procedures and all participants provided written informed consent prior to any procedures.

Background The natural history of airway inflammation and symptoms in occupations at risk of asthma is still not fully understood. We aimed to study the evolution during apprenticeship of inflammation markers, bronchial hyperresponsiveness (BHR) and symptoms in at-risk subgroups as defined from measurements of markers made shortly after the start of training. Methods Respiratory symptoms, FEV1 and airway resistance post-bronchial challenge (MBC) test results, fractional exhaled nitric oxide (FeNO) measurements, and eosinophils in nasal lavage fluid were investigated in apprentice bakers, pastry-makers and hairdressers. Four visits were conducted: at the start of the training and every six months thereafter. Four baseline risk groups were defined, based on, (i) a high level of FeNO (NO), (ii) eosinophils > 1% (Eosino), (iii) a ≥ 15% decrease in FEV1 during the MBC test (HR), and (iv) a ≥ 50% increase in the resistance (Resist). The statistical analysis relied on mixed models. Results At baseline, the inflammation markers were related to the MBC markers. There was no evidence to suggest that the baseline risk groups predict a differential evolution of the airway inflammation and bronchial responsiveness markers, or the asthma-like symptoms considered. The baseline risk groups defined from MBC test predicted the levels of MBC markers. Similarly, the baseline risk groups based on eosinophilic inflammation predicted the levels of markers for eosinophilia. These results were similar in the three training tracks, with the exception of the FeNO levels which were not different according to the Eosino risk group. Twelve possible new asthma cases were identified, only the HR risk group predicted their occurrence. Conclusions Among this young population, at-risk groups based on initial high levels of inflammation markers did not experience any worsening during the follow-up. However, initial BHR predicted consistently high levels of all markers considered and occurrence of possible asthma. Electronic supplementary material The online version of this article (10.1186/s12890-018-0674-9) contains supplementary material, which is available to authorized users.

Respiratory medicine relies both on clinical information and on complementary, laboratory tests results. However, despite today’s technological wonders, a proper history and a sound physical examination have no substitute as the initial step in making a correct diagnosis and, by consequence, providing the appropriate treatment. Respiratory complaints are frequently the cause that brings a patient to the doctor, and the respiratory system is the most commonly affected organ system in clinical practice. Consequently, respiratory sounds, either heard at a distance or auscultated over the chest, are integral to the evaluation of patients and may provide valuable clues. This chapter focuses on lung sounds as they are reported by patients (or by their guardians in the case of young children) and as a sign noted on chest auscultation performed with the stethoscope. The characteristics and the pathogenesis of adventitious breath sounds (stridor, wheeze, crackles, squawk) are briefly addressed and their clinical usefulness is discussed; voice-transmitted sounds and noisy breathing (grunt, snuffle, rattle, snore) are also presented. The four clinical cases included at the end of this chapter highlight the value of the proper understanding of breath sounds.

International audience; BACKGROUND: Atopy has emerged as a major determinant of airway inflammation.OBJECTIVE: To examine whether early markers of occupational asthma increase with degree of sensitisation.METHOD: This study was a prospective follow-up study of apprentices in baking, pastry-cooking and hairdressing during their 2-year apprenticeship. Four visits were conducted to administer a standardised questionnaire, a methacholine challenge test to assess bronchial hyperresponsiveness (BHR) and to measure fractional exhaled nitric oxide (FeNO). Degree of sensitisation was estimated based on the number of positive skin prick tests (SPTs) for 12 common allergens. Mixed-effect models were applied to examine the association between the degree of sensitisation and FeNO levels, BHR and eosinophilic status (more than 3% of cells in nasal lavage fluid).RESULTS: Of the 441 apprentices who agreed to take part in the study, 417 had at least one SPT session providing usable results. Degree of sensitization was related to BHR and FeNO levels. Compared to non-sensitised subjects, FeNO levels were 83% higher (P < 0.01) in highly sensitised subjects and 30% higher (P < 0.01) in weakly sensitised subjects. However, the degree of sensitisation was not predictive of the evolution of these markers.CONCLUSION: Degree of sensitisation is related to early markers of airway inflammation.

The natural history of airway inflammation and symptoms in occupations at risk of asthma is still not fully understood. We aimed to study the evolution during apprenticeship of inflammation markers, bronchial hyperresponsiveness (BHR) and symptoms in at-risk subgroups as defined from measurements of markers made shortly after the start of training.Respiratory symptoms, FEV1and airway resistance post-bronchial challenge (MBC) test results, fractional exhaled nitric oxide (FeNO) measurements, and eosinophils in nasal lavage fluid were longitudinally investigated in apprentice bakers, pastry-makers and hairdressers. Four baseline risk groups were defined, based on, (i) a high level of FeNO (NO), (ii) eosinophils>1% (Eosino), (iii) a≥15% decrease in FEV1during the MBC test (HR), and (iv) a≥50% increase in the resistance (Resist). The statistical analysis relied on mixed models.At baseline, the inflammation markers were related to the MBC markers. There was no evidence to suggest that the baseline risk groups predict a differential evolution of the airway inflammation and bronchial responsiveness markers, or the asthma-like symptoms considered. The baseline risk groups defined from MBC test predicted the levels of MBC markers. Similarly, the baseline risk groups based on eosinophilic inflammation predicted the levels of markers for eosinophilia. Twelve possible new asthma cases were identified, only the HR risk group predicted their occurrence.Among this young population, at-risk groups based on initial high levels of inflammation markers did not experience any worsening during the follow-up. Initial BHR predicted consistently high levels of all markers considered and occurrence of possible asthma. These results have been published in BMC Pulmonary Medicine (Demangeet al. BMC Pulm Med. 2018 July 11;18(1):113).

Background: The rates of optimal asthma control and compliance to treatment in Israel are reportedly low. We postulated that adults attending our emergency department (ED) with asthma exacerbation were not using self-management strategies optimally. Objectives: This pilot study aims to: (a) verify the above hypothesis and, if applicable, (b) determine whether an asthma education intervention (AEI) administered in the ED would encourage post-discharge use of a written asthma action plan (AAP). Methods: Thirty-eight adults (>18 yr.) visiting the ED with asthma exacerbation received a 30-min AEI including a written AAP. Prior asthma education was assessed by questionnaire. Follow-up, carried out by phone ≥ 12 months after discharge, assessed AAP use, asthma control (GINA), and exacerbations in the past year. Results: At baseline, participants denied previous education on asthma selfmanagement and AAP use. Of 27 patients available for follow-up, only 5 (18.5%) were using the AAP, assisted by their care-provider. Eighteen subjects (66.7%) presented uncontrolled asthma while, as a whole, the group reported significantly more exacerbation episodes than at enrolment (mean (SD)=5.1 (6.5) vs. 2.7 (3.0) (p=0.0498)). Finally, compared with AAP non-users (n=22) AAP users (n=5) tended to have better asthma control (60% vs. 18%) and fewer episodes of exacerbations (mean (SD)=2.8 (2.2) vs 5.9 (6.9)) but the differences did not reach significance. Conclusion: Delivery to adults of a short AEI in the ED was of limited efficiency in post-discharge boosting of patient/doctor partnership, resulting in sub-optimal AAP use. Feasibility of the AEI in a crowded ED, however, justifies further research on AEI delivery coupled with alternative follow-up strategies targeting patient and doctor perception of AAPs.

Background Most smokers start smoking during adolescence and become dependent before 20 years old. In France, vocational trainees are a population not much explored. The objective of our study is to present tobacco use characteristics among apprentices in Vocational Centers (VC). Methods This cross-sectional exhaustive study covered 1814 students (among whose 943 smokers) entering in a 1st year of the eight participating Vocational Centers in the Lorraine region (Eastern France, 2.3 million inhabitants, 16,500 vocational trainees), during the school years 2007–2008 and 2008–2009. Data collection concerned the sociocultural environment, tobacco use habits, degree of dependency to tobacco and co-addictions. Results Among the study population, 52.0% declared they were smokers among whom 89.4% daily smokers, and 5.7% were ex-smokers. The average age of tobacco use initiation was 12.1 years (standard deviation [SD] = 2.1) and the average age at inception of regular cigarette smoking was 13.8 years (SD = 1.6). Current consumption of the smokers was 12.8 cigarettes per day (SD = 7.8). The average score of smoking addiction was 6.1 (SD = 2.8), according to the Hooked On Nicotine checklist test (score from 0 to 10 = strongly dependent). Finally, 37.1% of students (58.9% among smokers) smoked or have smoked cannabis. Conclusion The high prevalence of smoking in Vocational Centers, the early start of tobacco use and the high tobacco consumption among apprentices show that they are overexposed compared to the general population of adolescents. In addition, these young people are already dependant to tobacco use. This underlines the need of specific measures dedicated to this population that amounts to 361,500 individuals in France.

Airway inflammation is a hallmark of asthma. Several studies have validated the use of the fractional concentration of exhaled nitric oxide (Fe(NO)) as a surrogate marker of airway inflammation in asthma.We examined how the change in Fe(NO) levels, since the beginning of occupational exposure, could be associated with the incidence of bronchial hyperresponsiveness (BHR) among baker, pastry maker, and hairdresser apprentices during their 2-year training.A standardized questionnaire was administered; skin prick tests for common and specific occupational allergens were done; methacholine challenge and measurement of Fe(NO) were performed 6, 12, and 15 months after the first examination.Of 441 apprentices initially included, 351 completed the study. The increase in Fe(NO), since the beginning of exposure, was associated with the incidence of BHR (odds ratio, 2.00 [95% confidence interval, 1.21-3.32] per unit increase in log parts per billion) both in atopic and nonatopic subjects. The average increase in Fe(NO) was similar in atopic and nonatopic subjects and was unrelated to past or current smoking habits, sex, or training track. Atopy in bakers/pastry makers and sensitization to alkaline persulfates in hairdressers were also independently associated with the incidence of BHR. BHR occurred sooner among bakers/pastry makers than among hairdressers, but its incidence leveled off later.Our results suggest that measurement of Fe(NO), a simple and reproducible test, could be useful in the screening of BHR in workers newly exposed to agents known to cause occupational asthma.

Background: COPD is a leading cause of mortality and morbidity. Early identification might be important in order to implement early interventions. This can help preventing exacerbations, preserve lung function and quality of life, and decrease mortality. Aims: To identify smokers with pre-bronchodilator airflow obstruction, who are considered to be at high-risk for the development of COPD. Methods: Smokers aged 35 years or older were screened. All of them performed pre-bronchodilator pulmonary function test (PFT). A standardized, 5-question questionnaire on smoking status and pulmonary symptoms was administered. (a simple score between 1-5 was given to according to symptoms: cough, sputum, shortness of breath). Those with evidence of abnormal PFT were referred for further medical assistance. Correlation between the questionnaire and PFT was done. Results: Three hundred twenty eight smokers were screened. 240 were males (73.2%) and 88 were women (26.8%). Suspected airflow obstruction defined as FEV1/FVC 80%), 24 had moderate obstruction (50% Conclusions: Obstruction in PFT was common (present in 17.1% of the smokers). A simple questionnaire was strongly correlated to airflow obstruction. This questionnaire might become a screening tool to detect COPD among smokers.

Methacholine $ \dot{\rm V} $ challenge testing (MCT) is widely used to assess airway hyperresponsiveness (AHR). Traditionally, a 20% or greater decline in forced expiratory volume in 1 (FEV1) is the primary outcome measure. We examined whether the inclusion of wheeze detection as outcome measure influenced the categorical interpretation of MCT in workers at risk of occupational asthma (OA). We examined 28 occupationally exposed smokers with asthma-like symptoms (SympAsth), 22 asymptomatic, occupationally exposed smokers (Symp0), and 30 nonexposed, asymptomatic controls (Ctrl). MCT was done using an abbreviated technique. Spirometry and tracheal wheezes were recorded using a computerized system. MCT was considered either positive or negative using three outcome measures separately: (1) ≥ 20% fall in FEV1 (MCT“FEV1”); (2) wheeze appearance (MCT“Wheeze”); and (3) whichever among the two was present (MCT“FEV1Wheeze”). The proportion of reactors in each group were, by outcome measure, as follows: MCT“FEV1”: Ctrl = 2 (6.7%), Symp0 = 6 (27.3%), SympAsth = l2 (42.8%) (χ2 = 10.2; p = 0.006); MCT“Wheeze”: Ctrl = 1 (3.3%), Symp0 = 4 (18.2%), SympAsth = 13 (46.4%) (χ2 = l5.7; p = 0.001); MCT“FEV1Wheeze” Ctrl = 2 (6.7%), Symp0 = 7 (31.8%), SympAsth = 18 (64.3%) (χ2 = 21.5; p = 0.001). Overall, including wheeze detection increased the proportion of “reactors” detected by spirometry by 30% (27 reactors vs. 20). This increase reached 50% (18 vs. 12) among workers with asthma like symptoms. In summary, the inclusion of wheeze detection as outcome measure for MCT allowed the recognition as reactors of subjects that otherwise would be “missed” by spirometry. The resulting increase in the number of true positives improved the sensitivity of MCT to detect AHR in occupationally exposed workers at risk of occupational asthma.

Background Spirometry is not routinely performed in smoking cessation trials. Smokers with airflow obstruction who are unavailable for follow-up incur the risk of accelerated loss in lung function. We evaluated the prevalence of airflow obstruction among smokers enrolled in smoking cessation trials and the proportion of subjects with obstruction unavailable for follow-up. Design, setting, and participants The study was performed in a university research laboratory; 598 smokers participating in two smoking cessation trials were included. All subjects underwent spirometry at entry and after 1 year of follow-up. All received nicotine replacement therapy. At completion, they were classified into quitters, reducers, or continuing smokers. Measurements and results At enrollment, spirometry findings were normal in 493 subjects (82.4%). Airway obstruction (FEV 1 1 70 to 80% predicted) in 75 subjects, moderate obstruction (FEV 1 50 to 69% predicted) in 22 subjects, and severe obstruction (FEV 1 Conclusions Spirometry detected a high prevalence yield of airflow obstruction in participants in smoking cessation trials. Most subjects with airflow obstruction were unavailable for follow-up; they would have remained unaware of their condition if not for spirometry. Smokers with airflow obstruction should be identified and advised to seek further care.

Resume Introduction Le tabagisme environnemental est un facteur de morbidite et de mortalite actuellement reconnu. Les premieres victimes sont les enfants, et ce quelquefois des leur conception, mais les adultes ne sont pas epargnes. En pratique, l’evaluation de l’exposition a la fumee de tabac peut etre realisee par des marqueurs biologiques plus ou moins specifiques du tabac. Etat des connaissances L’exposition fœtale au tabagisme maternel et le tabagisme environnemental de l’enfant peuvent avoir des repercussions tres graves qui engagent directement le pronostic vital du fœtus et du nourrisson. Il augmente le risque d’avortement spontane, de grossesse extra-uterine, de retard de croissance intra-uterin, de rupture prematuree des membranes, de prematurite, d’hematome retro-placentaire, de placenta praevia et de mort subite du nourrisson. Les pathologies respiratoires et cardiovasculaires chez l’adulte sont egalement influencees par le tabagisme environnemental. En France, le tabagisme passif provoque la mort prematuree de 3 000 personnes par an. Perspectives Une meilleure connaissance des risques lies a l’exposition au tabagisme passif devrait faciliter l’application de la legislation dont l’un des principaux objectifs est de proteger les non-fumeurs. Conclusions La prevention du tabagisme ainsi que l’aide au sevrage tabagique ne peuvent se concevoir sans une meilleure application de la loi Evin.

Women are less successful than men at quitting smoking. We examined whether the male vs. female cessation outcome was influenced by baseline smoking behavior in participants who attempted to quit by using nicotine inhaler (NI) plus nicotine patch (NP) combination therapy. This double-blind, randomized, placebo-controlled trial enrolled 196 men and 204 women. Group 1 (99 men, 101 women) received NI plus NP (15 mg nicotine/16 h) for 6 weeks, then NI plus placebo patch (PP) for 6 weeks, then NI alone for 14 weeks. Group 2 (97 men, 103 women) received NI plus PP for 12 weeks, then NI alone for 14 weeks. Outcome measures were continuous self-reported abstinence and expired carbon monoxide concentration < 10 ppm. Baseline nicotine dependence was assessed by the Fagerstrom Test for Nicotine Dependence (FTND), and behavioral dependence by the 18-question Glover-Nilsson Smoking Behavioral Questionnaire (GN-SBQ). Male vs. female complete abstinence rates, regardless of treatment group, were 61.7% vs. 46.6% at 6 weeks (p = .0022), 42.3% vs. 30.9% at 12 weeks (p = .017), 30.1% vs. 17.6% at 6 months (p = .003), and 23.0% vs. 10.8% at 12 months, respectively (p = .001). Men had significantly higher baseline FTND (p = .0180) and lower total GN-SBQ (p < .0001) scores than women. In conclusion, women appear to have higher behavioral, and lower nicotine, dependence than men according to the GN-SBQ and the FTND; thus both nicotine and behavioral treatment should be tailored to women to increase their chances of abstinence.

Background There is no unanimous agreement on the use of a diluent step to preface methacholine challenge testing. The "pros" for this step are that it allows a better training of the patient; the "cons" are that it requires additional time and effort. Objective We examined if there were any systematic effects when either the baseline or postdiluent (saline) forced expiratory volume in 1 second (FEV 1 ) was used to define the reactivity status. Methods All methacholine challenge tests performed during a 1-year period by a group of occupationally exposed workers (n = 183) were examined. Results The mean percentage change in FEV 1 from baseline to postsaline was −1.44 (± 3.47)% and the mean absolute change was −0.043 (± 0.11) L ( P 1 from baseline were −12.7% and +10.9%, respectively. Three subjects had a fall in FEV 1 after saline of 10% or more and were not given methacholine. From the remaining 180 subjects, 172 were equally classified as reactors (n = 67) or nonreactors (n = 105), both by baseline FEV 1 and postsaline FEV 1 . Eight subjects were classified as reactors by baseline FEV 1 but as nonreactors by saline FEV 1 . In these subjects, the average FEV 1 dropped 4.9% from baseline to saline and 17.3% from saline to end-test; thus, the total FEV 1 drop (22.5%) exceeded the 20% required for the test to be positive. Among reactors, no relationship was found between the response to saline and the subsequent response to methacholine ( r = 0.13). Conclusions Our data did not provide evidence to support the compulsory use of a diluent step when measuring bronchial responsiveness in populations. In general, the diluent step added time and expense to the test and, on occasion, forced a greater absolute drop in FEV 1 than is needed to demonstrate bronchial hyperresponsiveness.

OBJECTIVES—To investigate the relation between levels of cumulative exposure to wood dust and respiratory symptoms and the occurrence of bronchial hyperresponsiveness among beech and oak workers. METHODS—114 Male woodworkers from five furniture factories and 13 male unexposed controls were examined. The unexposed control group was supplemented by 200 male historical controls. Statistical analyses were performed excluding and including the historical controls. Dust concentration was measured by personal sampling methods. Cumulative exposure to dust was calculated for each woodworker by multiplying the duration of the work by the intensity of exposure (years.mg/m3). Bronchial hyperresponsiveness was assessed by the methacholine bronchial challenge test. Subjects were labelled methacholine bronchial challenge positive if forced expiratory volume in 1 second (FEV1) fell by ⩾20%. The linear dose-response slope was calculated as the last dose divided by the total dose given. RESULTS—443 Dust samples were collected. The median cumulative exposure to dust was 110 years.mg/m3 with lower and upper quartiles at 70 and 160 years.mg/m3 Overall, no declines in FEV1 and forced vital capacity (FVC) were found with increasing exposures. A dose-response relation was found between intensity of exposure on the one hand, and sore throat, increased prevalence of positive methacholine bronchial challenge tests, and steeper dose-response slope, on the other. CONCLUSION—Exposure to oak and beech dust may lead to the development of sore throat and bronchial hyperresponsiveness. Keywords: bronchial hyperresponsiveness; wood dust; beech; oak

Because some authors have reported high rates of failure in performing the single breath N2 (SBN2) test in rural areas, the present study aimed at evaluating its acceptability in a female population, unfamiliar with lung function testing, in a rural area of northeastern France. Two hundred ninety-eight women from a rural area volunteered for a preventive medicine examination (91.6% of those invited); four of them were excluded for clinical reasons, and six (2%) were unable to perform spirometry. The protocol included completion of a questionnaire, spirometry with a bronchial reactivity test, skin prick test, and the SBN2 test utilizing a computerized assembly. Although failures caused by the apparatus were few (n = 7, 2.4%) 96 of 281 women (34.1%) were unable to produce two valid SBN2 tests in a series of six attempts. Compared with the group who succeeded in the test (n = 185), women who failed were older and had a higher prevalence of bronchial hyperresponsiveness. Logistic regression confirmed the independent association of these two variables with an inability to perform. We conclude that in a female population completely unfamiliar with lung function testing the SBN2 test has a high rate of failure associated with higher age and the presence of bronchial hyperresponsiveness.

In population studies, the provocative dose (PD) of bronchoconstrictor causing a significant decrement in lung function cannot be calculated for most subjects. Dose-response curves for carbachol were examined to determine whether this relationship can be summarized by means of a continuous index likely to be calculable for all subjects, namely the two-point dose response slope (DRS) of mean resistance (Rm) and resistance at 10 Hz (R10) measured by the forced oscillation technique (FOT). Five doses of carbachol (320 microg each) were inhaled by 71 patients referred for investigation of asthma (n=16), chronic cough (n=15), nasal polyposis (n=8), chronic rhinitis (n=8), dyspnoea (n=8), urticaria (n=5), post-anaphylactic shock (n=4) and miscellaneous conditions (n=7). FOT resistance and forced expiratory volume in one second (FEV1) were measured in close succession. The PD of carbachol leading to a fall in FEV1 > or = 20% (PD20) or a rise in Rm or R10 > or = 47% (PD47,Rm and PD47,R10) were calculated by interpolation. DRS for FEV1 (DRSFEV1), Rm (DRSRm) and R10 (DRSR10) were obtained as the percentage change at last dose divided by the total dose of carbachol. The sensitivity (Se) and specificity (Sp) of DRSRm, DRS10 delta%Rm and delta%R10 in detecting spirometric bronchial hyperresponsiveness (BHR, fall in FEV1 > or = 20%) were assessed by receiver operating characteristic (ROC) curves. There were 23 (32%) "spirometric" reactors. PD20 correlated strongly with DRSFEV1 (r=-0.962; p=0.0001); PD47,Rm correlated significantly with DRSRm (r=-0.648; p=0.0001) and PD47,R10 with DRSR10 (r=-0.552; p=0.0001). DRSFEV1 correlated significantly with both DRSRm (r=0.700; p=0.0001) and DRSR10 (r=0.784; p=0.0001). The Se and Sp of the various FOT indices to correctly detect spirometric BHR were as follows: DRSRm: Se=91.3%, Sp=81.2%; DRSR10: Se=91.3%, Sp=95.8%; delta%Rm: Se=86.9%, Sp=52.1%; and delta%R10: Se=91.3%, Sp=58.3%. Dose-response slopes of indices of forced oscillation technique resistance, especially the dose-response slope of resistance at 10Hz are proposed as simple quantitative indices of bronchial responsiveness which can be calculated for all subjects and that may be useful in occupational epidemiology.

Study objectives: To verify that sick building symptoms are present in north-eastern France office workers; to try to identify new confounding factors. Methods: The design was that of a cross-sectional study with control group.We studied with the same methods the personnel of an air-conditioned building (n = 425), and of a naturally ventilated building (n = 351). Air temperature and humidity, bacterial and fungal densities were measured by the same technical staff in the two buildings. A standard questionnaire on irritative and respiratory symptoms, personal and family history, and lifestyle was completed by the participants. Results: In univariate analysis, exposure to air-conditioning was associated with an increased prevalence of symptoms (odds ratios-OR-between 1.54 and 2.84). A significant increase in sickness absence was also found among subects working in air-conditioned offices. As a series of factors were suspected to interfere with these associations, logistic regression was applied. This method confirmed exposure to be an independent determinant of 7 symptoms, and also identified two determinants not previously described: a family history of respiratory diseases and “do-it-yourself” activities. In Conclusion: we found the sick building symptoms to be present in a group of French office workers exposed to air-conditioning. We confirmed the influence of a number of confounding factors and described two further confounders – do-it-yourself activities at home and a history of familial respiratory disease.

OBJECTIVES: To assess the relation between measured levels of exposure to soluble oil mists in a plant manufacturing ball bearings, and both respiratory symptoms and airway responsiveness in the workforce. METHODS: 114 male workers exposed to oil mist and 55 unexposed male controls from nearby factories were studied. Soluble oil mist concentrations were measured with area samplers. Respiratory symptoms were assessed by questionnaire and measurement of airway responsiveness to methacholine with an abbreviated method. Subjects were labelled positive to methacholine airway challenge (MAC+) if forced expiratory volume in one second (FEV1) fell by > or = 20%. The linear dose-response slope was calculated as the percentage fall in FEV1 at the last dose divided by the total dose given. RESULTS: Geometric mean concentrations of oil mists ranged from 0.65 mg/m3 (GSD 1.29) to 2.20 mg/m3 (GSD 1.55) based on 92 measurements obtained from 1979-93. The prevalence of chronic cough or phlegm, bouts of bronchitis, and dyspnoea was greater among exposed workers than among controls (odds ratio (OR) 4.64, P = 0.002 for chronic cough and phlegm). After adjustment for smoking and age, dyspnoea was significantly related to an index of cumulative exposure to oil mist (OR 1.44, P = 0.006/10 y.mg/m3). The proportion of MAC+ subjects was similar in the two groups. However, after adjustment for baseline FEV1 and age, the dose-response slope was significantly steeper among exposed workers than among controls (P = 0.01), a finding indicating airway hyperresponsiveness in the exposed workers. Furthermore, the dose-response slope was significantly related to baseline FEV1, age, and, after adjustment for FEV1, the index of cumulative exposure to oil (P = 0.004). CONCLUSION: Subjects with exposure to soluble oil mist in the metal industry are at risk of developing both respiratory symptoms and airway hyperresponsiveness.

Background The influence of genetic predictors of inflammation and atopy on occupational asthma in apprentices is not known. Objectives To assess the influence of genetic polymorphisms of IL4RA , IL13 , TNFA , IL1A , and IL5 on the decline of lung function and bronchial hyperresponsiveness in a prospective follow-up study of baker/pastry maker and hairdresser apprentices. Methods A total of 351 apprentices were included in the study. We performed skin testing, spirometry, fractional exhaled nitric oxide measurement, and methacholine hyperreactivity testing at the initial visit and during and at the end of the 18-month training period. Gene variants of IL4RA, IL13, TNFA, IL1A , and IL5 were determined in DNA from nasal lavage. Results IL13 R130Q /IL4RA S478P or IL13 R130Q//IL4RA Q551R were significant predictors of the decrease of forced expiratory volume and forced vital capacity ( P ≤ .006). Genotype GG of TNFAG308A was associated with bronchial hyperresponsiveness in the whole population and in nonatopic individuals (90.63% vs 9.38%; odds ratio, 3.78; 95% confidence interval, 1.10-12.83). TNFA GA and IL5 CC and TNFA GA and IL1A CC were 2 epistatic predictors of exhaled nitrogen monoxide decrease during follow-up ( P = .02 and P = .004, respectively). The association with TNFA GA and IL1A CC was the most significant in nonatopic bakers ( P Conclusion We evidenced a predicting influence of IL13/IL4RA and TNFA in the early exposure to allergens and irritants that precedes occupational asthma. The significance of the associations in the absence of atopy suggests an influence of the genetics predictors related to inflammatory pathways.

Methacholine airway challenge (MAC) is a simple and useful means to assess bronchial hyperreactivity in workers exposed to various occupational hazards. Recently, wheeze detection by tracheal auscultation has been proposed as an indicator of bronchial responsiveness during bronchial provocation test in children. Our aim was to examine the relationship between the appearance of wheezes and the concurrent changes in forced expiratory volume in one second (FEV1) observed during MAC test in adults. Three cumulative doses of a methacholine solution (100 micrograms, 500 micrograms and 1500 micrograms) were inhaled by 45 workers with occupational exposure to flour dust. Spirometry was done using an electronic spirometer. Tracheal sounds were recorded with an electronic stethoscope placed over the anterior cervical triangle, 2 cm above the sternal notch. The amplified sounds were stored on magnetic tape, band-pass filtered (50-2000 Hz), and digitized at a sampling rate of 4096 Hz into a GenRad Vibration Control System. Wheezes were detected by fast Fourier transform (FFT) analysis and their presence compared to a 20% fall in FEV1. A positive MAC test by spirometry was found in 12 subjects whereas wheezes were identified in 14 subjects. Among the wheezing subjects, nine had a positive MAC test (range of fall in FEV1 = 20.6 to 42.3%) and five had a negative one (range of fall in FEV1 = 3.6 to 16.9%). Moreover, no wheezes were found in the remaining three subjects with a positive MAC test (range of fall in FEV1 = 20.7 to 27.4%). Taking a 20% fall in FEV1 as reference, wheezes were 75% sensitive and 84.8% specific to detect airflow obstruction. In conclusion, since it carries a significant although small false-negative rate, the acoustic technique based upon wheeze detection cannot, at the present time, fully replace spirometry during airway challenge testing in subjects with suspected asthma.

International audience; BACKGROUND: Exposure to pollutants in bakeries and hairdressing salons can cause airway syndromes varying from bronchial irritation to asthma. Workplace respiratory health surveillance aims to identify possible cases requiring further investigation. AIMS: To compare the performance of fractional exhaled nitric oxide (FE(NO)) and spirometry for health surveillance of apprentice bakers (ABs) and apprentice hairdressers (AHDs). Determinants of FE(NO) were also identified. METHODS: Symptoms and physician-diagnosed asthma were evaluated by questionnaire. FE(NO) was measured and spirometry was carried out. Subjects with elevated FE(NO) (FE(NO) > upper limit normal), airway obstruction [forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) < 95th percentile] and atopy (history of allergies) were identified. RESULTS: A total of 126 apprentices (59 ABs and 67 AHDs) participated. Twenty-nine (23%) apprentices had abnormal tests: 4 had associated high FE(NO) and airway obstruction, while 25 had either high FE(NO) (n = 15) or airway obstruction (n = 10) alone. Compared with ABs (n = 16), AHDs (n = 13) had more asthma (38 versus 0%; P < 0.05) and atopy (62 versus 6%; P < 0.05). There was no difference in symptoms, smoking FE(NO) or airways obstruction. Among 97 subjects with normal tests, no differences existed between ABs (n = 53) and AHDs (n = 44). Average FE(NO) was increased in atopic non-smokers compared with atopic smokers and non-atopic subjects (P < 0.05). Smoking, a history of allergies, FEV(1)/FVC % observed and respiratory symptoms were the main determinants of FE(NO). CONCLUSIONS: FE(NO) and spirometry were not overlapping dimensions in ABs and hairdressers, each test contributing unique information on the physiological status of the respiratory system. FE(NO) may provide added information on airway inflammation not provided by spirometry.

Computer-assisted techniques allow detailed analysis of the acoustic and physiological aspects of lung sounds. This short review of classic lung sounds includes both audio clips and interpretations made in the light of modern pulmonary acoustics.

Background Bronchial Hyperresponsiveness (BHR) is considered a hallmark of asthma. Other methods are helpful in epidemiological respiratory health studies including Fractional Exhaled Nitric Oxide (FENO) and Eosinophils Percentage (EP) in nasal lavage fluid measuring markers for airway inflammation along with the Forced Oscillatory Technique measuring Airway resistance (AR). Can their outcomes discriminate profiles of respiratory health in healthy subjects starting apprenticeship in occupations with a risk of asthma? Methods Rhinoconjunctivitis, asthma-like symptoms, FEV1 and AR post-Methacholine Bronchial Challenge (MBC) test results, FENO measurements and EP were all investigated in apprentice bakers, pastry-makers and hairdressers not suffering from asthma. Multiple Correspondence Analysis (MCA) was simultaneously conducted in relation to these groups and this generated a synthetic partition (EI). Associations between groups of subjects based on BHR and EI respectively, as well as risk factors, symptoms and investigations were also assessed. Results Among the 441 apprentice subjects, 45 (10%) declared rhinoconjunctivitis-like symptoms, 18 (4%) declared asthma-like symptoms and 26 (6%) suffered from BHR. The mean increase in AR post-MBC test was 21% (sd = 20.8%). The median of FENO values was 12.6 ppb (2.6-132 range). Twenty-six subjects (6.7%) had EP exceeding 14%. BHR was associated with atopy (p < 0.01) and highest FENO values (p = 0.09). EI identified 39 subjects with eosinophilic inflammation (highest values of FENO and eosinophils), which was associated with BHR and atopy. Conclusions Are any of the identified markers predictive of increased inflammatory responsiveness or of development of symptoms caused by occupational exposures? Analysis of population follow-up will attempt to answer this question.

Background Most of the efforts to reduce teenagers' tobacco addiction have focused on smoking prevention and little on smoking cessation. A smoking cessation program (TABADO study), associating pharmacologic and cognitive-behavioural strategy, on a particularly vulnerable population (vocational trainees), was developed. This study aims to evaluate the efficacy of the program which was offered to all smokers in a population aged 15 to 20 years in Vocational Training Centers (VTC). This paper presents the TABADO study protocol. Methods The study is quasi-experimental, prospective, evaluative and comparative and takes place during the 2 years of vocational training. The final population will be composed of 2000 trainees entering a VTC in Lorraine, France, during the 2008-2009 period. The intervention group (1000 trainees) benefited from the TABADO program while no specific intervention took place in the "control" group (1000 trainees) other than the treatment and education services usually available. Our primary outcome will be the tobacco abstinence rate at 12 months. Discussion If the program proves effective, it will be a new tool in the action against smoking in populations that have been seldom targeted until now. In addition, the approach could be expanded to other young subjects from socially disadvantaged backgrounds in the context of a public health policy against smoking among adolescents. Trial registration Clinical trial identification number is NTC00973570.

BackgroundOccupational asthma is a common type of asthma caused by a specific agent in the workplace. The basic alteration of occupational asthma is airways inflammation. Although most patients with occupational asthma are mature adults, there is evidence that airways inflammation starts soon after inception of exposure, including during apprenticeship. Airways hyper responsiveness to methacholine is a valid surrogate marker of airways inflammation, which has proved useful in occupational epidemiology. But it is time-consuming, requires active subject's cooperation and is not readily feasible. Other non-invasive and potentially more useful tests include the forced oscillation technique, measurement of fraction exhaled nitric oxide, and eosinophils count in nasal lavage fluid.Methods and designThis study aims to investigate early development of airways inflammation and asthma-like symptoms in apprentice bakers, pastry-makers and hairdressers, three populations at risk of occupational asthma whose work-related exposures involve agents of different nature. The objectives are to (i) examine the performance of the non-invasive tests cited above in detecting early airways inflammation that might eventually develop into occupational asthma; and (ii) evaluate whether, and how, constitutional (e.g. atopy) and behavioural (e.g. smoking) risk factors for occupational asthma modulate the effects of allergenic and/or irritative substances involved in these occupations. This paper presents the study rationale and detailed protocol.DiscussionAmong 441 volunteers included at the first visit, 354 attended the fourth one. Drop outs were investigated and showed unrelated to the study outcome. Sample size and follow-up participation rates suggest that the data collected in this study will allow it to meet its objectives.

Background Airway inflammation and airway hyperresponsiveness (AHR) are two characteristic features of asthma. Fractional exhaled nitric oxide (FENO) has shown good correlation with AHR in asthmatics. Less information is available about FENO as a marker of inflammation from work exposures. We thus examined the relation between FENO and AHR in lifeguards undergoing exposure to chloramines in indoor pools. Methods 39 lifeguards at six indoor pools were given a respiratory health questionnaire, FENO measurements, spirometry, and a methacholine bronchial challenge (MBC) test. Subjects were labeled MBC+ if the forced expiratory volume (FEV1) fell by 20% or more. The normalized linear dose-response slope (NDRS) was calculated as the percentage fall in FEV1 at the last dose divided by the total dose given. The relation between MBC and FENO was assessed using logistic regression adjusting on confounding factors. The association between NDRS and log-transformed values of FENO was tested in a multiple linear regression model. Results The prevalence of lifeguards MBC+ was 37.5%. In reactors, the median FENO was 18.9 ppb (90% of the predicted value) vs. 12.5 ppb (73% predicted) in non-reactors. FENO values ≥ 60% of predicted values were 80% sensitive and 42% specific to identify subjects MBC+. In the logistic regression model no other factor had an effect on MBC after adjusting for FENO. In the linear regression model, NDRS was significantly predicted by log FENO. Conclusions In lifeguards working in indoor swimming pools, elevated FENO levels are associated with increased airway responsiveness.

Tobacco use is dominated by cigarette smoking. Most toxicity due to cigarette smoking is related to the burning process. Several observations suggest that unburned or oral tobacco is less harmful than cigarette smoking. Up to now, physicians have advised a policy based on two ideas: (i) young people should not start smoking and (ii) the only choice for smokers is to quit. However, numerous smokers cannot or do not want to give up; eventually, one out of two lifelong smokers will die from smoke-related diseases. Thus, it is legitimate to ask if alternate nicotine containing product use would be better than cigarette smoking and limit the tobacco death toll. However, the logic leading to the concept of tobacco harm reduction (THR) turns out to be much more complex than it looks at a first glance.

Studies over the past few decades have showed a clear association between cigarette smoking and the development of chronic airway obstruction. Yet, only a minority of smokers is affected so that in many, even heavy, smokers, pulmonary function remains within normal limits. While carcinogens have been well characterized, there is only limited information about the constituents of cigarette smoke responsible for inducing chronic airway obstruction. In addition, the associated risks factors for airway obstruction in smokers have not been totally identified. The present paper is a review of the recently accumulated facts concerning the intimate action of cigarette smoke at the level of large and small airways and lung parenchyma. The role of classical inflammatory cells such as neutrophils and alveolar macrophages is reviewed, but emphasis is put on recent evidence indicating the involvement of CD8+ T-lymphocytes and possibly eosinophils in the genesis of the structural changes leading to airways obstruction. The mechanisms by which airway inflammation and remodelling cause airway narrowing and airflow limitation are discussed, along with the associated loss of lung elasticity secondary to destructive emphysema. Other biological, epidemiological, physiopathological, and clinical aspects are analyzed, stressing such fundamental aspects as the defence mechanisms, the morpho-functional correlations, the identification of susceptible smokers, and the early detection of airway obstruction, both in specialized laboratories and in primary care.

Asthma has a tendency, to destabilize and get worse at night, probably due to a nocturnal increase in airiway inflammation and bronchial responsiveness. Nocturnal airway narrowing in asthma is often associated with sleep disorders, such as episodes of nocturnal and early morning awakening, difficulty in maintaining sleep, and day time sleepiness. On the other hand, an association has been documented between nocturnal sleep-disordered breathing and asthma. This review highlights the causes of nocturnal worsening of asthma and examines the evidence pointing toward a causal relationship between nocturnal asthma and sleep-disordered breathing.

To the Editor: We describe a woman with Behcet's syndrome characterized by recurrent oral and genital aphthous ulcers, severe eye involvement, and the onset of arthritis at the age of 29 years. She had started smoking at the age of 17 and regularly smoked 20 cigarettes a day (total history of smoking, approximately 20 pack-years). At the age of 35, during a remission of symptoms of Behcet's syndrome, she stopped smoking without the use of nicotine-replacement therapy. Within two weeks after she had quit, several large and extremely painful buccal aphthous ulcers developed, with no genital involvement. These ulcerations were . . .

There is only limited information on the factors associated with nonspecific bronchial hyperresponsiveness (BHR) in farmers. Our purpose was to examine the relationship between BHR and respiratory symptoms, atopy, and abnormalities of lung function in a sample of French farmers. Farmers scheduled for a preventive medicine check-up in northeastern France were examined. Occupational exposure, respiratory symptoms, and work-related symptoms were assessed by questionnaire, sensitization to 34 common and agricultural allergens by skin prick tests, and BHR by the single-dose (1,200 microg) acetylcholine (ACh) challenge test. Data were obtained from 741 farmers (95% of those invited). Seventy-seven subjects (10.3%) had BHR defined as a fall in forced expiratory volume in 1 s (FEV1)/= 10% after the inhalation of ACh or, for those with a poor lung function, an increase in FEV110% and200 ml after the inhalation of 200 microg of salbutamol. The proportion of asthmalike symptoms, especially wheeze during work, positive skin tests to acarian (storage mites) and cereal dust allergens, and low levels of lung function was significantly greater among reactors than among nonreactors. Stepwise logistic regression analysis showed a significant and independent association between BHR and wheezing during work (OR = 4.99; 95% CI = 2.29-10.89; p = 0.0001) and baseline FEV1 (OR = 1.49; 95% CI = 1.05-2.20; p = 0.026). In conclusion, hyperreactive farmers had significantly more asthmalike symptoms, positive skin tests, and abnormal lung function than normoreactive farmers. Work-related wheeze and low baseline FEV1 were significantly and independently associated with BHR.

OBJECTIVES: To measure the levels of exposure to nitrogen trichloride (NCl3) in the atmosphere of indoor swimming pools and to examine how they relate to irritant and chronic respiratory symptoms, indices of pulmonary function, and bronchial hyperresponsiveness to methacholine in lifeguards working in the pools. METHOD: 334 lifeguards (256 men; 78 women) recruited from 46 public swimming pools (n = 228) and 17 leisure centre swimming pools (n = 106) were examined. Concentrations of NCl3 were measured with area samplers. Symptoms were assessed by questionnaire and methacholine bronchial challenge (MBC) test by an abbreviated method. Subjects were labelled MBC+ if forced expiratory volume in one second (FEV1) fell by > or = 20%. The linear dose- response slope was calculated as the percentage fall in FEV1 at the last dose divided by the total dose given. RESULTS: 1262 samples were taken in the 63 pools. Mean NCl3 concentrations were greater in leisure than in public pools. A significant concentration-response relation was found between irritant eye, nasal, and throat symptoms-but not chronic respiratory symptoms-and exposure concentrations. Among women, the prevalence of MBC+ was twice as great as in men. Overall, no relation was found between bronchial hyperresponsiveness and exposure. CONCLUSIONS: The data show that lifeguards exposed to NCl3 in indoor swimming pools are at risk of developing irritant eye, nasal, and throat symptoms. Exposure to NCl3 does not seem to carry the risk of developing permanent bronchial hyperresponsiveness, but this association might have been influenced by self selection. The possibility that subjects exposed to NCl3 are at risk of developing transient bronchial hyperresponsiveness cannot be confidently ruled out.