Treatment and outcomes of patients with chronic lung disease and acute myocardial infarction: Insights from the nationwide AMIS plus registry.

BACKGROUND: Limited data are available on patients with chronic lung disease (CLD) presenting with acute myocardial infarction (AMI). We aimed to analyse baseline characteristics, treatment and outcome of those patients enrolled in the Swiss nationwide prospective AMIS Plus registry. METHODS: All AMI patients enrolled between January 2002 and December 2021 with data on CLD, as defined in the Charlson Comorbidity Index, were included. The primary endpoints were in-hospital mortality and major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, reinfarction and cerebrovascular events. Baseline characteristics, in-hospital treatments and outcomes were analysed using descriptive statistics and logistic regression. RESULTS: Among 53,680 AMI patients enrolled during this time, 5.8% had CLD. Compared with patients without CLD, CLD patients presented more frequently with non-ST-elevation myocardial infarction (MI) and type 2 MI (12.8% vs. 6.5%, p < 0.001). With respect to treatment, CLD patients were less likely to receive P2Y12 inhibitors (p < 0.001) and less likely to undergo percutaneous coronary interventions (68.7% vs. 82.5%; p < 0.001). In-hospital mortality declined in AMI patients with CLD over time (from 12% in 2002 to 7.3% in 2021). Multivariable regression analysis showed that CLD was an independent predictor for MACCE (adjusted OR was 1.28 [95% CI 1.07-1.52], p = 0.006). CONCLUSION: Patients with CLD and AMI were less likely to receive evidence-based pharmacologic treatments, coronary revascularization and had a higher incidence of MACCE during their hospital stay compared to those without CLD. Over 20 years, in-hospital mortality was significantly reduced in AMI patients, especially in those with CLD.

Telehealth mitigates COPD disease progression compared to standard of care: a randomized controlled crossover trial.

BACKGROUND: We showed excellent adherence and satisfaction with our telehealth care (TC) approach for COPD. Here, the results of a consecutive randomized controlled trial are presented. METHODS: Patients were randomly assigned to TC or standard care (SC). During TC, patients answered six daily questions online, and focused on the early recognition of exacerbations, in addition to SC. RESULTS: The mean increase in COPD assessment test (CAT) was 1.8 vs. 3.6 points/year in the TC and SC groups, respectively (P = 0.0015). Satisfaction with care (VAS) at baseline was 8.2; at the end of SC, 8.5 (P = 0.062); and after TC, 8.8 (P < 0.001). We detected significantly more moderate exacerbations during TC. CONCLUSION: Whilst receiving TC, the slope of the CAT increase - an indicator of the naturally progressive course of COPD - was reduced by 50%. Satisfaction with care increased with TC. The higher number of detected moderate exacerbations probably indicates a higher diagnostic sensitivity than without TC.

Length of hospital stay for TB varies with comorbidity and hospital location.

BACKGROUND: Although most guidelines overwhelmingly recommend outpatient TB treatment, hospitalisations are common. We investigated the proportion of TB patients hospitalised and determined factors associated with length of stay (LOS) in Switzerland.METHODS: Cases with TB as the primary diagnosis were retrieved from a nation-wide hospitalisation database and compared to TB notifications. Month and year of admission, hospital site, type of TB, age, sex, LOS and up to 50 ICD-10 coded comorbidities were compared with controls matched for age, sex and admission date.RESULTS: From 2002 to 2015, the estimated TB hospitalisation rate was 81%. The median LOS of 6,234 TB patients was stable at 14 days (IQR 6-22), but increased in patients with miliary TB, old patients and with hospital location. TB-associated comorbidities included HIV, liver disease, anaemia, malnutrition and genitourinary tract diseases. LOS was associated with three comorbidity clusters: 1) malnutrition, cachexia and anaemia (median LOS 20 days, IQR 13-31); 2) toxic liver disease and hepatitis (median LOS 23 days, IQR 14-37.5); and 3) adverse drug events (median LOS 20 days, IQR 13-30).CONCLUSION: Most TB patients were hospitalised. LOS was related to TB type, comorbidities and hospital location. Promoting outpatient care is a priority to improve TB management in Switzerland.

Erlotinib has comparable clinical efficacy to chemotherapy in pretreated patients with advanced non-small cell lung cancer (NSCLC): A propensity-adjusted, outcomes research-based study.

OBJECTIVES: Controversy exists about the integration of erlotinib in patients with EGFR wildtype, advanced NSCLC. MATERIALS AND METHODS: We included patients with advanced NSCLC receiving at least two lines of palliative systemic treatment between January 2005 and December 2014 and not harbouring targetable driver mutations. Primary study endpoint was overall survival (OS), secondary endpoint progression-free survival (PFS). We used Kaplan-Meier statistics, multivariate Cox regression and Propensity score or Inverse Probability Weights (IPW) matching to compare clinical outcome between patients receiving erlotinib in second or further line and those receiving chemotherapy only. The study had a power of 90% to detect a survival superiority of 30%. RESULTS: From a total of 827 patients, we excluded 171 patients with potentially curative treatment, 189 receiving treatment outside of our institute, 206 receiving no or only one line of systemic treatment, 6 with ALK translocations and 28 with EGFR mutations. From 227 patients in the final efficacy analysis, 125 patients received erlotinib in second (89 patients), third (28) or further-line (8), and 102 patients received chemotherapy only. Women and never smokers were significantly overrepresented in the erlotinib group. Both OS (hazard ratio (HR)=1.14, 95% CI 0.80-1.63, P=0.448) and PFS (HR=1.20, 95% CI 0.95-1.52, P=0.119) were similar in the erlotinib compared to the chemotherapy group using IPW-adjusted Cox regression analysis treating the use of erlotinib as a time-dependent covariate starting from second-line treatment and stratified for ECOG performance status and treatment line. ECOG performance status was the most powerful covariate to select patients for erlotinib treatment. CONCLUSION: The present study suggests erlotinib to have similar clinical efficacy compared to chemotherapy in patients with pretreated advanced NSCLC and no known molecular targetable alterations.

[The role of chronic or transient hypoxia on the retinal nerve fiber layers]. / Die Rolle einer chronischen oder einer transienten Hypoxie auf die retinalen Nervenfaserschichten.

BACKGROUND: In a clinical study, the role of chronic hypoxia in patients with chronic obstructive pulmonary disease or the role of transient hypoxia in patients with obstructive sleep apnea syndrome were examined for the peripapillary retinal nerve fiber layers. PATIENTS AND METHODS: 10 patients with chronic obstructive pulmonary disease GOLD stages 3 or 4 (4 men and 6 women, age 47 to 71 years, mean 60.6 years) and 10 patients with obstructive sleep apnea syndrome with an apnea-hypopnea index of 15 or more (8 men and 2 women, age 39 to 76 years, mean 60.7 years) were included in the study. The thickness of the retinal nerve fiber layers was measured with an optical coherence tomography. RESULTS: In the group with chronic obstructive pulmonary disease and in the group with obstructive sleep apnea syndrome, the measurements of the retinal nerve fiber layers were in normal range. CONCLUSIONS: By using optical coherence tomography, no lesions to the retinal nerve fiber layers were detectable in patients with chronic or transient hypoxia. The findings of the study could be limited by the too short duration of the disease and/or to the too small number of patients.

[ARDS after Incidental Aspiration of Petroleum in an Adult]. / ARDS nach akzidentieller Aspiration von Petroleum bei einem Erwachsenen.

Petroleum aspiration as a reason for lipid pneumonia is a rare complication. Mostly children are affected and mortality rates are low. In most case series, virtually every subject survived.We describe here the case of a patient who developed ARDS and pneumatoceles with a fatal outcome. Due to the undulant nature of the disease, multipe thoracic CT were performed, enabling us to describe the precise radiologic course of the disease.

Physical activity and the frequency of acute exacerbations in patients with chronic obstructive pulmonary disease.

PURPOSE: Acute exacerbations (AE) in patients with COPD are associated with a decline in lung function, increased risk of hospitalization, and mortality. In this cross-sectional study we tested whether the level of objectively measured daily physical activity and exercise capacity are associated with the number of COPD exacerbations. METHODS: In 210 patients with COPD (67 % men; mean (SD) age: 63 (8) years) enrolled in The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland (TOPDOCS) physical activity (PA) (steps per day, physical activity level, (PAL)), exercise capacity (6-min walking distance, (6MWD)), comorbidities, lung function, and medication were assessed. Differences between COPD patients with frequent (≥2 year) and infrequent (0-1 year) exacerbations were assessed. Univariate and multivariate analyses were performed to investigate whether the level of objectively measured daily physical activity and exercise capacity are associated with the number of COPD exacerbations. RESULTS: Patients with frequent AE had a significantly lower FEV1 and 6MWD compared to patients with infrequent AE. In univariate analysis, the number of exacerbations was inversely associated with FEV1, 6MWD, BMI, and smoking status while there was a positive association with RV/TLC and combined inhaled medication. However, there was no significant association with PAL and steps per day. In multivariate analysis, FEV1 and the use of combined inhaled medication were independently associated with the number of AE, after correction for covariates. CONCLUSIONS: The findings of this study imply that FEV1, independent of inhaled medication, is significantly associated with COPD exacerbations. Neither physical activity nor exercise capacity was independently associated with COPD exacerbations.

Circulating microRNA profiling in patients with advanced non-squamous NSCLC receiving bevacizumab/erlotinib followed by platinum-based chemotherapy at progression (SAKK 19/05).

OBJECTIVES: Molecular subclassification of non small-cell lung cancer (NSCLC) is essential to improve clinical outcome. This study assessed the prognostic and predictive value of circulating micro-RNA (miRNA) in patients with non-squamous NSCLC enrolled in the phase II SAKK (Swiss Group for Clinical Cancer Research) trial 19/05, receiving uniform treatment with first-line bevacizumab and erlotinib followed by platinum-based chemotherapy at progression. MATERIALS AND METHODS: Fifty patients with baseline and 24 h blood samples were included from SAKK 19/05. The primary study endpoint was to identify prognostic (overall survival, OS) miRNA's. Patient samples were analyzed with Agilent human miRNA 8x60K microarrays, each glass slide formatted with eight high-definition 60K arrays. Each array contained 40 probes targeting each of the 1347 miRNA. Data preprocessing included quantile normalization using robust multi-array average (RMA) algorithm. Prognostic and predictive miRNA expression profiles were identified by Spearman's rank correlation test (percentage tumor shrinkage) or log-rank testing (for time-to-event endpoints). RESULTS: Data preprocessing kept 49 patients and 424 miRNA for further analysis. Ten miRNA's were significantly associated with OS, with hsa-miR-29a being the strongest prognostic marker (HR=6.44, 95%-CI 2.39-17.33). Patients with high has-miR-29a expression had a significantly lower survival at 10 months compared to patients with a low expression (54% versus 83%). Six out of the 10 miRNA's (hsa-miRN-29a, hsa-miR-542-5p, hsa-miR-502-3p, hsa-miR-376a, hsa-miR-500a, hsa-miR-424) were insensitive to perturbations according to jackknife cross-validation on their HR for OS. The respective principal component analysis (PCA) defined a meta-miRNA signature including the same 6 miRNA's, resulting in a HR of 0.66 (95%-CI 0.53-0.82). CONCLUSION: Cell-free circulating miRNA-profiling successfully identified a highly prognostic 6-gene signature in patients with advanced non-squamous NSCLC. Circulating miRNA profiling should further be validated in external cohorts for the selection and monitoring of systemic treatment in patients with advanced NSCLC.

Characteristics of medically and surgically treated empyema patients: a retrospective cohort study.

BACKGROUND: The role of drainage, intrapleural fibrinolytics, and/or surgery in the management of thoracic empyema is controversial. OBJECTIVES: We aimed to investigate the operational practice of empyema management at our hospital. METHODS: Between January 2001 and December 2008, all patients with thoracic empyema were retrieved. After exclusion of patients with malignant effusion, traumatic or iatrogenic empyema, and a history of pleurodesis or tuberculosis, we compared the characteristics of medically versus surgically treated empyema patients. RESULTS: Seventy-eight of 215 retrieved patients were acute bacterial empyema cases. All received intravenous antibiotics. Fifty-eight (74.4%) initially received tube thoracostomy, 34 (43.6%) were treated with intrapleural urokinase, and 30 (38.5%) were operated on. Of 20 patients without initial tube thoracostomy, 15 (75%) were operated on, compared to 9 (37.5%) who were initially treated by tube thoracostomy without intrapleural fibrinolytics (OR 5; 95% CI 1.4-18.5, p = 0.01) and 6 (17.7%) who were initially treated with tube thoracostomy and intrapleural urokinase (OR 14; 95% CI 3.6-53.6, p < 0.001). The surgery patients were not different in demographic and clinical characteristics but were more likely to describe significant chest pain 12 months after discharge. CONCLUSIONS: In this retrospective cohort study of thoracic empyema patients, initial chest tube insertion and intrapleural fibrinolytics were associated with less surgical therapy. Other predictors of the need for surgery could not be identified. Surgery patients were more likely to suffer from residual chest pain 12 months after discharge. Initial treatment with IV antibiotics, chest tube, and intrapleural fibrinolytics was successful in the majority of patients.

Diagnosis and management of chronic obstructive pulmonary disease: the Swiss guidelines. Official guidelines of the Swiss Respiratory Society.

The new Swiss Chronic Obstructive Pulmonary Disease (COPD) Guidelines are based on a previous version, which was published 10 years ago. The Swiss Respiratory Society felt the need to update the previous document due to new knowledge and novel therapeutic developments about this prevalent and important disease. The recommendations and statements are based on the available literature, on other national guidelines and, in particular, on the GOLD (Global Initiative for Chronic Obstructive Lung Disease) report. Our aim is to advise pulmonary physicians, general practitioners and other health care workers on the early detection and diagnosis, prevention, best symptomatic control, and avoidance of COPD as well as its complications and deterioration.

Determinants of change in airway reactivity over 11 years in the SAPALDIA population study.

We investigated determinants of change in bronchial reactivity in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA), a population-based cohort with wide age range (29-72 yrs at follow-up). The role of sex, age, atopic status, smoking and body mass index (BMI) on percentage change in bronchial reactivity slope from the baseline value was analysed in 3,005 participants with methacholine tests in 1991 and 2002, and complete covariate data. Slope was defined as percentage decline in forced expiratory volume in 1 s from its maximal value per micromole of methacholine. Bronchial hyperreactivity prevalence fell from 14.3 to 12.5% during follow-up. Baseline age was nonlinearly associated with change in reactivity slope: participants aged <50 yrs experienced a decline and those above an increase during follow-up. Atopy was not associated with change, but accentuated the age pattern (p-value for interaction = 0.038). Smoking significantly increased slope by 21.2%, as did weight gain (2.7% increase per BMI unit). Compared with persistent smokers, those who ceased smoking before baseline or during follow-up experienced a significant decrease in slope (-27.7 and -23.9%, respectively). Differing, but not statistically different, age relationships and effect sizes for smoking and BMI between sexes were found. Mean bronchial reactivity increases after 50 yrs of age, possibly due to airway remodelling or ventilation-perfusion disturbances related to cumulative lifetime exposures.

Prevalence of airflow obstruction in smokers and never-smokers in Switzerland.

The aim of the present study was to measure age-specific prevalence of airflow obstruction in Switzerland in smokers and never-smokers using pulmonary function tests and respiratory symptoms from 6,126 subjects participating in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults. The lower limit of normal of the forced expiratory volume in 1 s/forced vital capacity ratio was used to define airflow obstruction. Severity of airflow obstruction was graded according to the recommendations of the Global Initiative for Chronic Obstructive Lung Disease. Prevalence of airflow obstruction ranged from 2.5% in subjects aged 30-39 yrs to 8.0% in those aged ≥ 70 yrs. In multivariate analysis, age (OR 2.8, ≥ 70 yrs versus 30-39 yrs), smoking (OR 1.8) and asthma (OR 6.7) were associated with airflow obstruction. Never-smokers constituted 29.3% of subjects with airflow obstruction. Never-smokers with airflow obstruction were younger, more likely to be male and reported asthma more frequently than obstructive smokers. Obstructive smokers and never-smokers had similar level of symptoms and quality of life impairment. The prevalence of airflow obstruction in Switzerland is similar to other developed countries. Never-smokers account for a third of the prevalence, which is higher proportion than elsewhere. Airflow obstruction in never-smokers deserves attention because of its frequency and its similar health impact to that in smokers.

Longitudinal change of prebronchodilator spirometric obstruction and health outcomes: results from the SAPALDIA cohort.

BACKGROUND: Understanding the prognostic meaning of early stages of chronic obstructive pulmonary disease (COPD) in the general population is relevant for discussions about underdiagnosis. To date, COPD prevalence and incidence have often been estimated using prebrochodilation spirometry instead of postbronchodilation spirometry. In the SAPALDIA (Swiss Study on Air Pollution and Lung Disease in Adults) cohort, time course, clinical relevance and determinants of severity stages of obstruction were investigated using prebronchodilator spirometry. METHODS: Incident obstruction was defined as an FEV(1)/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio >or=0.70 at baseline and <0.70 at follow-up, and non-persistence was defined inversely. Determinants were assessed in 5490 adults with spirometry and respiratory symptom data in 1991 and 2002 using Poisson regression controlling for self-declared asthma and wheezing. Change in obstruction severity (defined analogously to the GOLD (Global Initiative for Chronic Obstructive Lung Disease) classification) over 11 years was related to shortness of breath and health service utilisation for respiratory problems by logistic models. RESULTS: The incidence rate of obstruction was 14.2 cases/1000 person years. 20.9% of obstructive cases (n = 113/540) were non-persistent. Age, smoking, chronic bronchitis and non-current asthma were determinants of incidence. After adjustment for asthma, only progressive stage I or persistent stage II obstruction was associated with shortness of breath (OR 1.71, 95% CI 0.83 to 3.54; OR 3.11, 95% CI 1.50 to 6.42, respectively) and health service utilisation for respiratory problems (OR 2.49, 95% CI 1.02 to 6.10; OR 4.17 95% CI 1.91 to 9.13, respectively) at follow-up. CONCLUSIONS: The observed non-persistence of obstruction suggests that prebronchodilation spirometry, as used in epidemiological studies, might misclassify COPD. Future epidemiological studies should consider both prebronchodilation and postbronchodilation measurements and take specific clinical factors related to asthma and COPD into consideration for estimation of disease burden and prediction of health outcomes.

Effectiveness of a procalcitonin algorithm to guide antibiotic therapy in respiratory tract infections outside of study conditions: a post-study survey.

All published evidence on procalcitonin (PCT)-guided antibiotic therapy was obtained in trials where physicians knew that they were being monitored, possibly resulting in higher adherence to the PCT algorithm. This study investigates the effectiveness of PCT guidance in an observational quality control survey. We monitored antibiotic therapy and algorithm adherence in consecutive patients with respiratory tract infections admitted to the Kantonsspital Aarau, Switzerland, between May 2008 and February 2009. The results were compared to the site-specific results of the former ProHOSP study. Overall and more pronounced for patients with community-acquired pneumonia, the median duration of antibiotic treatment in this survey was shorter than the ProHOSP control patients (6 vs. 7 days, P = 0.048 and 7 vs. 9 days, P < 0.001). In 72.5% of patients, antibiotics were administered according to the prespecified PCT algorithm. No significant differences concerning adverse medical outcome could be detected. This study mirrors the use of PCT-guided antibiotic therapy in clinical practice, outside of trial conditions. If algorithm adherence is reinforced, antibiotic exposure can be markedly reduced with subsequent reduction of antibiotic-associated side effects and antibiotic resistance. The integration of the PCT algorithm into daily practice requires ongoing reinforcement and involves a learning process of the prescribing physicians.

Prevalence of sarcoidosis in Switzerland is associated with environmental factors.

The current study aimed to investigate incidence, prevalence and regional distribution of sarcoidosis in Switzerland with respect to environmental exposures. All sarcoidosis patients hospitalised between 2002 and 2005 were identified from the Swiss hospital statistics from the Swiss Federal Office for Statistics (Neuchâtel, Switzerland). Regional exposure characteristics included the regional distribution of different industrial sectors, agriculture and air quality. Co-inertia analysis, as well as a generalised linear model, was applied. The prevalence of "ever-in-life" diagnosed sarcoidosis, currently active sarcoidosis and sarcoidosis requiring hospitalisation was 121 (95% CI 93-149), 44 (95% CI 34-54) and 16 (95% CI 10-22) per 100,000 inhabitants, respectively. The mean annual incidence of sarcoidosis was 7 (95% CI 5-11) per 100,000 inhabitants. The regional workforce in the metal industry, water supply, air transport factories and the area of potato production, artificial meadows (grassland) and bread grains were positively associated with the frequency of sarcoidosis. The prevalence of sarcoidosis was higher than assumed based on former international estimates. Higher frequency was found in regions with metal industry and intense agriculture, especially production of potatoes, bread grains and artificial meadows.

B-type natriuretic peptide and C-terminal-pro-endothelin-1 for the prediction of severely impaired peak oxygen consumption.

OBJECTIVE: To assess the utility of B-type natriuretic peptide (BNP) and C-terminal-pro-endothelin-1 (CT-proET-1) to predict a severely impaired peak oxygen consumption (peak VO(2), < 14 mL kg(-1) min(-1)) in patients referred for cardiopulmonary exercise testing. DESIGN: Cross-sectional study. SETTING: Tertiary care center. METHODS: Peak VO(2), BNP and CT-proET-1 were assessed in 141 consecutive patients referred for cardiopulmonary exercise testing. RESULTS: B-type natriuretic peptide [median (interquartile range) 48 (38-319) vs. 33 (15-86) pg mL(-1); P = 0.002] and CT-proET-1 [87 (76-95) vs. 60 (52-74) pmol L(-1); P < 0.001] were higher in patients with a peak VO(2) < 14 mL kg(-1) min(-1) (n = 30) than in those with a peak VO(2) > or = 14 mL kg(-1) min(-1) (n = 111). CT-pro-ET-1 had a higher area under the receiver-operator-characteristics curve (AUC) to predict a peak VO(2) < 14 mL kg(-1) min(-1) than BNP (0.79 vs. 0.68; P = 0.04). The optimal BNP cut-off of 37.2 pg mL(-1) had a sensitivity of 80% and a specificity of 56%. The optimal CT-proET-1 cut-off of 74.4 pmol L(-1) had a sensitivity of 80% and specificity of 76%. A five-item score composed of body mass index, diabetes, forced expiratory volume within the first second, alveolo-arterial oxygen pressure difference, and BNP had an AUC of 0.88 to predict a peak VO(2) < 14 mL kg(-1) min(-1). Adding CT-proET-1 to the score resulted in an AUC of 0.92. CONCLUSIONS: C-terminal-pro-endothelin-1 is superior to BNP for the prediction of a peak VO(2) < 14 mL kg(-1) min(-1) in patients referred for CPET. A score incorporating body mass index, diabetes status, spirometry, blood gases, BNP and CT-proET-1 improves the prediction of a peak VO(2) < 14 mL kg(-1) min(-1) based on single biomarkers.

A randomised, controlled trial of bosentan in severe COPD.

Pulmonary hypertension during exercise is common in severe chronic obstructive pulmonary disease (COPD). It was hypothesised that the use of the endothelin-receptor antagonist bosentan can improve cardiopulmonary haemodynamics during exercise, thus increasing exercise tolerance in patients with severe COPD. In the present double-blind, placebo-controlled study, 30 patients with severe or very severe COPD were randomly assigned in a 2:1 ratio to receive either bosentan or placebo for 12 weeks. The primary end-point was change in the 6-min walking distance. Secondary end-points included changes in health-related quality of life, lung function, cardiac haemodynamics, maximal oxygen uptake and pulmonary perfusion patterns. Compared with placebo, patients treated with bosentan during 12 weeks showed no significant improvement in exercise capacity as measured by the 6-min walking distance (mean+/-SD 331+/-123 versus 329+/-94 m). There was no change in lung function, pulmonary arterial pressure, maximal oxygen uptake or regional pulmonary perfusion pattern. In contrast, arterial oxygen pressure dropped, the alveolar-arterial gradient increased and quality of life deteriorated significantly in patients assigned bosentan. The oral administration of the endothelin receptor antagonist bosentan not only failed to improve exercise capacity but also deteriorated hypoxaemia and functional status in severe chronic obstructive pulmonary disease patients without severe pulmonary hypertension at rest.

Induction chemotherapy followed by parenchyma-sparing surgery in medically inoperable NSCLC-results of a feasibility study.

PURPOSE: Feasibility trial to test the toxicity and outcome of three cycles of induction chemotherapy followed by limited surgery in medically inoperable early stage NSCLC patients. PATIENTS AND METHODS: Thirteen patients with NSCLC (stages I-IIIB) with insufficient cardio-respiratory reserves for the oncologically required lung resection, received three cycles of induction chemotherapy with cisplatin (100mg/m(2)) and docetaxel (85mg/m(2)) followed by parenchyma-sparing lung surgery. Operability was evaluated with pulmonary function tests, perfusion scintigraphy and cardiopulmonary exercise testing. In selected patients coronary angiography or myocardial perfusion scintigraphy was performed. Rate of R0-resections was taken as primary outcome. RESULTS: Twelve of 13 patients received the three cycles of chemotherapy as planned. The main grade 3/4 hematological toxicity was neutropenia (62%), non-hematological toxicity was neutropenic fever (23%) and cough/dyspnea (31%). Complete, partial and stable responses to chemotherapy were seen in 1, 10 and 2 patients, respectively-the overall response rate was 85%. No patient had tumor progression. Eleven/13 (85% (CI 95% 54, 97) %) patients underwent surgery (4 lobectomies, 2 segmentectomies, and 5 wedge resections), all had a pathologically complete resection of the tumor. There was one postoperative death due to myocardial infarction. The median disease-free and overall survivals were 57(CI 95% 36-78) months and 66(CI 95% 40-92) months, with a median follow up time of 58 months. The 1-, 2- and 4-year OS was 85%, 85% and 67%, respectively. There were no significant changes in any lung function parameter compared to the preoperative assessment. The FEV(1) showed a trend for improved values after surgery. CONCLUSION: Induction chemotherapy in medically inoperable patients followed by parenchyma-sparing surgery is feasible and yields very promising results.

Glutathione S-transferase genotype increases risk of progression from bronchial hyperresponsiveness to asthma in adults.

BACKGROUND: Bronchial hyperresponsiveness (BHR) and variation in glutathione S-transferase (GST) genes have been associated with asthma risk. The relationship of these two risk factors with adult onset asthma in the general population was investigated. METHODS: GSTP1 Ile105Val single nucleotide polymorphism and GSTM1 and GSTT1 gene deletion polymorphisms were genotyped in the population-representative SAPALDIA cohort. BHR was assessed at baseline by methacholine challenge and defined as a fall of > or =20% in forced expiratory volume in 1 s. Independent effects of GST polymorphisms and BHR on new onset of asthma after 11 years of follow-up were estimated by multiple logistic regression analysis, adjusting for relevant baseline measures. Effect modification was assessed by including interaction terms in the model. RESULTS: Among 4426 asthma-free participants at baseline, 14% had BHR. At follow-up, 3.3% reported new onset of physician-diagnosed asthma. BHR (p<0.001) and GSTP1 Ile105Val genotype (p = 0.005) were independently associated with incident asthma, but no association was seen for GSTT1 and GSTM1 gene deletion polymorphisms. Among subjects free of respiratory symptoms at baseline, the effect of BHR on the risk of physician-diagnosed asthma at follow-up was restricted to GSTP1 105 Ile/Ile carriers (OR 4.57, 95% CI 2.43 to 8.57 vs 1.40, 95% CI 0.58 to 3.39; p for interaction = 0.023). CONCLUSIONS: If confirmed by independent studies, our results suggest that GSTP1 Ile105Val genotype strongly determines the progression of BHR to physician-diagnosed asthma in the general population.