Clinical Use of an Exposure, Symptom, and Spirometry Algorithm to Stratify Smokers into COPD Risk Phenotypes: A Case Finding Study Combined with Smoking Cessation Counseling.

Background: Chronic obstructive pulmonary disease (COPD) case-finding aims to detect airflow obstruction in symptomatic smokers and ex-smokers. We used a clinical algorithm including smoking, symptoms, and spirometry to classify smokers into COPD risk phenotypes. In addition, we evaluated the acceptability and effectiveness of including smoking cessation advice in the case-finding intervention. Methods: Smoking, symptoms, and spirometry abnormalities (airflow obstruction: forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] <0.7 or preserved-ratio spirometry (FEV1<80% of predicted value and FEV1/FVC ratio ≥ 0.7)] were assessed in a group of 864 smokers aged ≥ 30 years. The combination of these parameters allowed the identification of 4 phenotypes: Phenotype A (no symptoms, normal spirometry; reference), Phenotype B (symptoms; normal spirometry; possible COPD), Phenotype C (no symptoms; abnormal spirometry; possible COPD), and Phenotype D (symptoms; abnormal spirometry; probable COPD). We assessed phenotype differences in clinical variables and modeled the trend from phenotype A to phenotype D. Smoking cessation advice based on spirometry was provided. Follow-up was done by telephone 3 months later. Results: Using smokers without symptoms or abnormal spirometry (phenotype A; n=212 [24.5%]) as a reference, smokers were classified into possible COPD (phenotype B;n=332 [38.4%]; and C: n=81 [9.4%]) and probable COPD (phenotype D: n=239 [27.2%]). The trend from baseline phenotype A to probable COPD phenotype D was significant for the number of cigarettes/day and the number of years of smoking (p=0.0001). At follow-up, 58 (7.7%) of the respondents (n=749) reported that they had quit smoking. Conclusions: Our clinical algorithm allowed us to classify smokers into COPD phenotypes whose manifestations were associated with smoking intensity and to significantly increase the number of smokers screened for COPD. Smoking cessation advice was well accepted, resulting in a low but clinically significant quit rate.

Prevalence and Persistence of Symptoms in Adult COVID-19 Survivors 3 and 18 Months after Discharge from Hospital or Corona Hotels.

COVID-19 is characterized by persistent symptoms beyond acute illness. In this prospective cohort study of patients with COVID-19, we sought to characterize the prevalence and persistence of symptoms up to 18 months after diagnosis. We followed 166 patients and assessed their symptoms during acute illness, and at 3 and 18 months after disease onset. The mean number of symptoms per patient during acute disease was 2.3 (SD:1.2), dropping to 1.8 (SD:1.1) at 3 months after recovery and to 0.6 (SD:0.9) at 18 months after recovery. However, this decrease was not unidirectional. Between acute illness and 3 months, the frequency of symptoms decreased for cough (64.5%→24.7%), ageusia (21.7% to6%), anosmia (17.5%→5.4%), and generalized pain (10.8% to 5.4%) but increased for dyspnea (53%→57.2%) weakness (47%→54.8%), and brain fog (3%→8.4%). Between 3 and 18 months, the frequency of symptoms decreased for all symptoms but remained relatively high for dyspnea (15.8%), weakness (21.2%), and brain fog (7.3%). Symptoms may persist for at least 18 months after acute COVID-19 infection. During the medium- to long-term recovery period, the prevalence of some symptoms may decrease or remain stable, and the prevalence of others may increase before slowly decreasing thereafter. These data should be considered when planning post-acute care for these patients.

Varenicline for Gradual Versus Abrupt Smoking Cessation in Poorly Motivated Smokers With COPD: A Prematurely Terminated Randomized Controlled Trial.

Background: Although smoking is the leading cause of chronic obstructive pulmonary disease (COPD), many patients with COPD smoke, highlighting the need for effective smoking cessation interventions in this population. This study examined the efficacy and safety of varenicline in increasing smoking cessation rates through "gradual" versus "abrupt" cessation in COPD patients with low motivation to quit smoking. Methods: A randomized, open label, 30-week, controlled trial (ClinicalTrials.gov identifier: NCT02894957) was conducted between January 2019 and October 2020 at a center in Israel. Smokers with COPD, poorly motivated to quit, were randomized to 6 weeks of varenicline for smoking reduction and a target quit day (TQD) at the end of week 6 (gradual cessation group) or ad libitum smoking for 5 weeks, 1 week of varenicline, and a TQD at the end of week 6 (abrupt cessation group). After the pre-quit phase, both groups received 12-week regular varenicline treatment and 12-week follow-up. Primary outcome was biochemically-validated continuous abstinence for weeks 6-30. Secondary outcomes were: (1) biochemically-confirmed7-day point prevalence abstinence for weeks 4-30, (2) efficient smoking reduction (≥50% in number of cigarettes/day) in the pre-quit phase; and (3) number of cigarettes/day, motivation to quit, and changes in respiratory symptoms and spirometry from baseline through week 30. Results: A drug recall issued by the study sponsor stopped the study after 70/242 (28.9%) patients had been enrolled. The gradual cessation group (n=29) had significantly higher continuous abstinence rates from TQD through week 30 versus the abrupt cessation group (n=41): 20.7% versus 4.9% (odds ratio [OR]=5.09; 95% confidence interval [CI] 0.89-29.17; p=0.048) and higher 7-day point prevalence abstinence levels at all time points but week 18 (p=0.027 at week 6, 0.056 at week 7, and 0.096 at week 9). Motivation to quit increased (p=0.002) and the number of cigarettes/day decreased (p=0.002) over time in both groups. Respiratory symptoms, but not spirometry, improved in both groups at week 30. Treatment was safe and well tolerated. Conclusion: In poorly motivated smokers with COPD, using varenicline for a 6-week gradual smoking cessation before TQD, compared with abrupt cessation, significantly increased quit rates up to 6 months. Results were not affected by the smaller-than-expected sample size. Further studies are needed to confirm these data.

Early Detection of COPD: An Opportunistic Case Finding Study in Smokers and Ex-Smokers Visiting a Medical Centre.

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.

Influence of language skills on the choice of terms used to describe lung sounds in a language other than English: a cross-sectional survey of staff physicians, residents and medical students.

INTRODUCTION: The 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. OBJECTIVE: To examine the transfer to Hebrew-taken as a model of LOTE-of the recommended terminology in English. DESIGN/SETTING: Cross-sectional study; university-based hospital. PARTICIPANTS: 143 caregivers, including 31 staff physicians, 65 residents and 47 medical students. METHODS: Observers 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. RESULTS: Range (%) 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. CONCLUSION: Poor 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.

Influence of observer preferences and auscultatory skill on the choice of terms to describe lung sounds: a survey of staff physicians, residents and medical students.

BACKGROUND: In contrast with the technical progress of the stethoscope, lung sound terminology has remained confused, weakening the usefulness of auscultation. We examined how observer preferences regarding terminology and auscultatory skill influenced the choice of terms used to describe lung sounds. METHODS: Thirty-one staff physicians (SP), 65 residents (R) and 47 medical students (MS) spontaneously described the audio recordings of 5 lung sounds classified acoustically as: (1) normal breath sound; (2) wheezes; (3) crackles; (4) stridor and (5) pleural friction rub. A rating was considered correct if a correct term or synonym was used to describe it (term use ascribed to preference). The use of any incorrect terms was ascribed to deficient auscultatory skill. RESULTS: Rates of correct sound identification were: (i) normal breath sound: SP=21.4%; R=11.6%; MS=17.1%; (ii) wheezes: SP=82.8%; R=85.2%; MS=86.4%; (iii) crackles: SP=63%; R=68.5%; MS=70.7%; (iv) stridor: SP=92.8%; R=90%; MS=72.1% and (v) pleural friction rub: SP=35.7%; R=6.2%; MS=3.2%. The 3 groups used 66 descriptive terms: 17 were ascribed to preferences regarding terminology, and 49 to deficient auscultatory skill. Three-group agreement on use of a term occurred on 107 occasions: 70 involved correct terms (65.4%) and 37 (34.6%) incorrect ones. Rate of use of recommended terms, rather than accepted synonyms, was 100% for the wheezes and the stridor, 55% for the normal breath sound, 22% for the crackles and 14% for the pleural friction rub. CONCLUSIONS: The observers' ability to describe lung sounds was high for the wheezes and the stridor, fair for the crackles and poor for the normal breath sound and the pleural friction rub. Lack of auscultatory skill largely surpassed observer preference as a factor determining the choice of terminology. Wide dissemination of educational programs on lung auscultation (eg, self-learning via computer-assisted learning tools) is urgently needed to promote use of standardised lung sound terminology.

Extending varenicline preloading to 6 weeks facilitates smoking cessation: A single-site, randomised controlled trial.

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).

Identification of Asthma-COPD Overlap, Asthma, and Chronic Obstructive Pulmonary Disease Phenotypes in Patients with Airway Obstruction: Influence on Treatment Approach.

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] <0.7); and (ii) delineate the therapeutic approach of each group. 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 <0.70; (b) asthma: physician-diagnosed asthma before age 40 and/or minimum post-BD increase in FEV1 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.

Do airway inflammation and airway responsiveness markers at the start of apprenticeship predict their evolution during initial training? A longitudinal study among apprentice bakers, pastry makers and hairdressers.

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.

Symptom evaluation during the methacholine test: Does it add to the interpretation of the test results based on the PC20FEV1?

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 < 8 mg/mL), subjects were classified as asymptomatic non-responders (ANRs), asymptomatic responders (ARs), symptomatic non-responders (SNRs) and symptomatic responders (SRs). Airway responsiveness for all subjects, including non-responders (ie, fall in FEV1 < 20%), was assessed by the methacholine concentration response-slope (MCRS) obtained using all points of the curve. RESULTS: ARs (n = 6) were poor-perceivers of bronchoconstriction. SNRs (n = 16) did not differ from SRs (n = 34) in any clinical parameter, including the proportion of subjects (∼80%) whose methacholine test reproduced symptoms justifying referral. In turn, SNRs differed significantly from ANRs (n = 26) by having lower baseline FEV1 (P = .005), more physician-diagnosed asthma (P < .001), more use of respiratory medication (P = .032), and relatively greater responsiveness as manifested by a steeper MCRS (P < .001). CONCLUSIONS: The occurrence of asthma-like symptoms during the methacholine test was associated with milder airway hyperresponsiveness that would go unnoticed by the PC20FEV1. This finding suggests that SNRs should not be merely classified as having normal responsiveness, as currently recommended, but further assessed for airway inflammation. Our results helped planning a longitudinal study to investigate the prognostic validity of this approach.

Ectopic pancreatic pseudocyst and cyst presenting as a cervical and mediastinal mass: case report and review of the literature.

Ectopic pancreas in the mediastinum is extremely rare. We are reporting on a case of a twenty two year old woman who presented to our clinic with a large cervical mass. The CT scan revealed a cystic lesion in the anterior mediastinum. The patient underwent surgical resection by cervical approach. A Cystic mass with pseudocysts, cysts and complete pancreatic tissue were found in pathology. There were no signs of pancreatitis or malignancy. No recurrence was observed after a follow up of four years. We reviewed the case reports describing this rare condition in the medical literature.We conclude that the possibility of ectopic pancreatic tissue should be included in the differential diagnosis of anterior mediastinal cystic mass, though as a remote possibility. Surgery is probably needed for the diagnosis and treatment. Posterior mediastinal pseudocyst is a different entity associated with acute pancreatitis. In those cases surgery is not recommended. Our third conclusion is that pancreatic tissue should be actively sought, if a structure resembling a pseudocyst is found in an unexpected location. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1849369005957671.

Genetic predictors of inflammation in the risk of occupational asthma in young apprentices.

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 < .001). 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.

Efficacy of a smoking cessation program in a population of adolescent smokers in vocational schools: a public health evaluative controlled study.

BACKGROUND: To evaluate the public health efficacy of a community-based smoking cessation program (TABADO) among vocational school trainees (15 to 20 years old). METHODS: This prospective, controlled, quasi-experimental study was conducted in eight vocational training centres (VTC) in France. The intervention group underwent the TABADO program, which included a general information session for all students and small-group sessions plus individual counselling and nicotine therapy, if needed, for volunteers in an enhanced program. The control group received no specific intervention other than the educational services usually available. The primary outcome was 30-day point prevalence abstinence at 12 months. RESULTS: The mean age of the 1,814 students included was 16.9 years (SD = 1.0); 84.7% were males. At baseline, 52% were smokers and 5.7% ex-smokers. In the intervention group, 24.6% of smokers volunteered for the enhanced program and 18.1% could be included. By 12-month follow-up, with participants lost to follow-up considered non-abstinent, 10.6% of smokers in the intervention group had become abstinent versus 7.4% in the control group (adjusted p = 0.03; odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.05-3.0); considering lost to follow-up as missing data, 17% of intervention group participants were abstinent versus 11.9% in the control group (univariate p = 0.08; adjusted p = 0.008; OR = 2.1; 95% CI = 1.2-3.6). CONCLUSION: The TABADO program, targeting teenagers in vocational schools, was effective in producing a higher 12-month abstinence rate among all smokers in the intervention group. TRIAL REGISTRATION: Clinical trial identification number is NTC00973570.

Associations of airway inflammation and responsiveness markers in non asthmatic subjects at start of apprenticeship.

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.

Increase in exhaled nitric oxide is associated with bronchial hyperresponsiveness among apprentices.

RATIONALE: 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. OBJECTIVES: 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. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

TABADO: "evaluation of a smoking cessation program among adolescents in vocational training centers": study protocol.

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.