FeNO levels increase with degree of sensitisation in apprentices at risk of occupational asthma.

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.

[Tobacco use characteristics among apprentices in Vocational Centers]. / Caractéristiques du tabagisme chez les adolescents en Centre de formation des apprentis.

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.

Exhaled nitric oxide and spirometry in respiratory health surveillance.

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.

[Respiratory diseases related to passive smoking]. / Les pathologies respiratoires liées au tabagisme passif.

Passive smoking, measured in practice by using specific biomarkers, is a well known factor of morbidity and mortality. The main victims are children, often starting from conception, but adults are not spared. Many respiratory diseases are caused and/or worsened by passive smoking and environmental tobacco smoke (ETS) exposure can have serious health consequences that reduce life expectancy (sudden infant death, respiratory infections, asthma, chronic obstructive pulmonary diseases and lung cancer). Better knowledge of these risks has favourably influenced the legislation banning smoking in enclosed public places in France and in other countries. If one of the main objectives of this measure is to protect non-smokers as well as smokers, its rigorous application fits directly within the goals of prevention and treatment of tobacco dependency.

[Risk reduction strategies in smoking]. / La réduction de risque en tabacologie.

INTRODUCTION: Around the world, due to its high efficiency in delivering nicotine, cigarette is, by far, the first device used to consume tobacco. But, as far as health is concerned, cigarette is the worst nicotine delivery system and cleaner delivery systems would be welcome. In respect to tobacco smoking, up to now, most doctors have supported the "quit smoking or die" dogma. However, some smokers cannot or do not want to completely give up the consumption of nicotine. BACKGROUND: Indeed, while some smokers can stop smoking and, for some of them, simply switch to a nicotine replacement therapy (NRT), other smokers crave the acute effects associated with the rapid massive surge of nicotine delivered to the brain by tobacco smoke. Currently, this rapid nicotine "high" is mainly experienced by smoking cigarettes, thus explaining the high rate of smoking relapse. VIEWPOINT: Thus, for smokers who cannot totally give up nicotine, it is sound to evaluate the rationale for the use of tobacco products with possible lower toxicity than cigarette smoke. CONCLUSIONS: Unfortunately, this important question triggers off passionate statements, while scientific and experimental observations are still very tenuous. Furthermore, the tobacco companies, by producing new tobacco products and promoting the use of smokeless tobacco such as snus, put a constant pressure on the Public Health community.

[Passive smoking]. / Le tabagisme passif.

INTRODUCTION: Environmental tobacco smoke is a recognized factor of morbidity and mortality. The first victims are children, sometimes starting from conception, but adults are not spared. In practice, evaluation of exposure to tobacco smoke can be achieved with more or less specific markers of tobacco smoke. CURRENT KNOWLEDGE: Exposure of the fetus to maternal smoking and of the infant to environmental smoke can have a serious sometimes life-threatening impact. Such exposure increases the risk of spontaneous abortion, ectopic pregnancy, intrauterine growth retardation, premature membrane rupture, preterm birth, retroplacental hematoma, placenta praevia, and sudden infant death. Adult respiratory and cardiovascular disease are also influenced by environmental smoke. In France passive smoking causes premature death of 3000 persons per year. PERSPECTIVES: Better knowledge of the risks of exposure to passive smoking can facilitate application of legislation with the objective of protecting non-smokers. CONCLUSIONS: Rigorous application of current legislation is important to achieve the stated goals of prevention of smoking as well as assistance to cease smoking.

Mechanisms of chronic airway obstruction in smokers.

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.

Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Nicotine replacement therapy is an effective treatment for nicotine-dependent smokers. However, cessation rates are modest, and preliminary studies suggest that combination therapy may be superior. We compared the efficacy of the nicotine inhaler plus nicotine patch vs nicotine inhaler plus placebo patch for smoking cessation. METHODS: A double-blind, randomized, placebo-controlled trial was conducted in 400 subjects who had smoked 10 or more cigarettes per day for 3 years or longer. Group 1 (n = 200) received the nicotine inhaler plus nicotine patch (delivering 15 mg of nicotine per 16 hours) for 6 weeks, then inhaler plus placebo patch for 6 weeks, then inhaler alone for 14 weeks. Group 2 (n = 200) received the nicotine inhaler plus placebo patch for 12 weeks, then inhaler for 14 weeks. Inhaler was used at a rate of 6 to 12 cartridges per day ad libitum for 3 months and then tapered off. Main outcome measures were complete abstinence (self-reported) and expired carbon dioxide concentration less than 10 ppm. RESULTS: Group 1 vs group 2 complete abstinence rates were 60.5% and 47.5% at 6 weeks (P =.009), 42.0% and 31.0% at 12 weeks (P =.02), 25.0% and 22.5% at 6 months (P =.56), and 19.5% and 14.0% at 12 months (P =. 14). One-year survival analysis showed a significant association between abstinence and treatment with nicotine inhaler plus nicotine patch (P =.04). Mean nicotine substitution at week 6 was 60.1% (group 1) and 24.6% (group 2) (P<.001). At 12 months, the frequency of respiratory symptoms in abstinent subjects fell significantly and lung function showed a trend toward improvement. The most common adverse events were throat irritation (inhaler) and itching (patch). CONCLUSIONS: Treatment with the nicotine inhaler plus nicotine patch resulted in significantly higher cessation rates than inhaler plus placebo patch.

Symptoms, airway responsiveness, and exposure to dust in beech and oak wood workers.

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/m(3)). Bronchial hyperresponsiveness was assessed by the methacholine bronchial challenge test. Subjects were labelled methacholine bronchial challenge positive if forced expiratory volume in 1 second (FEV(1)) 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/m(3) with lower and upper quartiles at 70 and 160 years.mg/m(3) Overall, no declines in FEV(1) 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.

Age and bronchial hyperresponsiveness are associated with failure to perform the single breath N2 test in a rural female population.

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.

Bronchial hyperresponsiveness in farmers: relation to respiratory symptoms, lung function, and atopy.

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 FEV1 > 10% and > 200 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.

Dose-response slope of forced oscillation and forced expiratory parameters in bronchial challenge testing.

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.

Sick-building symptoms in office workers in northeastern France: a pilot study.

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 subjects 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.

Respiratory symptoms and bronchial responsiveness in lifeguards exposed to nitrogen trichloride in indoor swimming pools.

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.

Lung auscultation in airway challenge testing.

The appearance of wheezes and changes in inspiratory breath (vesicular) sound intensity (BSI) were monitored in patients undergoing routine methacholine challenge test (MCT). The results were compared with changes in spirometry and to airway hyper-responsiveness (AH). Fifty-four patients were examined. Spirometry was performed before and after the inhalation of cumulative doses of methacholine starting from 25 micrograms; a fall in forced expiratory volume in 1 s (FEV1) by 20% or more was considered as significant. Lung auscultation was performed by two observers simultaneously using a special stethoscope placed sequentially over the posterior right and left upper (interscapular region, 5 cm from the fourth thoracic vertebra) and lower lung zones (5 cm below the scapulae). Symptoms were recorded by the patients on a visual analogue scale. In 27 patients, the MCT was positive (MCT+) and in 27 patients it was negative (MCT-). Wheezes were identified at PD20 in 12 MCT+ patients while reduced BSI alone was found in 11 patients; in four patients, auscultation was normal. In 20 MCT+ patients, either wheezes, diminished BSI or both were heard, one to several steps before reaching PD20. In the MCT- group, wheezes were detected in two patients and diminished BSI in four. In MCT+ patients, the mean (+/-SD) perception of symptoms at end-challenge was 33% (+/-26), whereas in MCT- patients, it was 13.6% (+/-22). Complete inter-observer agreement was found in 95.7% of auscultations performed (Kappa coefficient = 0.846). Coupled to spirometry, lung auscultation may prove useful in airway challenge testing provided the concept is accepted that wheeze appearance and, by extension, an acute decrease in BSI, is as legitimate a manifestation of AH as a fall in FEV1.

Airway responsiveness, respiratory symptoms, and exposures to soluble oil mist in mechanical workers.

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.