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Genetic variants and risk of lung cancer in never smokers

This four-stage study systematically investigated common genetic variations associated with the risk of developing lung cancer in never smokers. Stage 1 involved a genome-wide association study at the Mayo Clinic. A total of 331 918 single nucleotide polymorphisms (SNPs) in 377 case–control matched pairs were analysed. The 44 most significant SNPs that might alter the risk of lung cancer in never smokers were selected. The MD Anderson Cancer Center and Harvard School of Public Health (n=735 and 335, respectively) tested these 44 most significant SNPs. The SNP rs2352028 (at 13q31.3) was the one most associated with lung cancer in never smokers. This finding was repeated in a replication cohort.

For all four studies the combined p value for the association between rs2352028 and lung cancer in never smokers was 5.94x10–6 (OR 1.46, 95% CI 1.26 to 1.70). 10% of lung cancer cases in never smokers could be attributed to genetic...

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes

Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods

To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up.

Results

Three COPD groups were identified: group 1 (n=126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV1) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n=125, 69 years) showed milder airflow limitation (FEV1 63% predicted); and group 3 (n=91, 67 years) combined a similarly milder airflow limitation (FEV1 58% predicted) with a high proportion of obesity, cardiovascular disorders, diabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p<0.001) and higher all-cause mortality (HR 2.36, p=0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p=0.014).

Conclusions

In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated: ‘severe respiratory COPD’, ‘moderate respiratory COPD’, and ‘systemic COPD’.

Complex sleep apnoea in congestive heart failure

Sleep disordered breathing is common and of prognostic significance in patients with congestive heart failure (CHF). Complex sleep apnoea (complexSA) is defined as the emergence of central sleep apnoea during continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnoea (OSA). This study aims to determine the prevalence and predictors for complexSA in patients with CHF with OSA, and to assess the effects of treatment with adaptive servoventilation.

Methods

192 patients with CHF (left ventricular ejection fraction (LVEF) ≤45%, New York Heart Association (NYHA) class ≥2) and OSA (apnoea–hypopnoea index (AHI) ≥15) were investigated using echocardiography, cardiopulmonary exercise testing, measurement of hyperoxic, hypercapnic ventilatory response, 6 min walk test and measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) prior to CPAP introduction. If patients demonstrated complexSA (AHI >15/h with <10% obstructive events) during CPAP titration, adaptive servoventilation was introduced and the investigations were repeated at 3 monthly follow-up visits.

Results

ComplexSA developed in 34 patients (18%) during CPAP titration. After adjustment for demographic and cardiac parameters, measures of CO2 sensitivity (higher hyperoxic, hypercapnic ventilatory response) were independently associated with complexSA. Patients using adaptive servoventilation had improved AHI, NYHA class, NT-proBNP concentration, LVEF, hyperoxic, hypercapnic ventilatory response, oxygen uptake during cardiopulmonary exercise testing and the relationship between minute ventilation and the rate of CO2 elimination (VE/Vco2 slope) at last individual follow-up (14±4 months).

Conclusion

There is a high prevalence of complexSA in patients with OSA and CHF, and those who develop complexSA have evidence of higher respiratory controller gain before application of CPAP. Treatment with adaptive servoventilation effectively suppressed complexSA and had positive effects on cardiac function and respiratory stability.

The COPD assessment test (CAT): response to pulmonary rehabilitation. A multicentre, prospective study

The COPD (chronic obstructive pulmonary disease) assessment test (CAT) is a recently introduced, simple to use patient-completed quality of life instrument that contains eight questions covering the impact of symptoms in COPD. It is not known how the CAT score performs in the context of clinical pulmonary rehabilitation (PR) programmes or what the minimum clinically important difference is.

Methods

The introduction of the CAT score as an outcome measure was prospectively studied by PR programmes across London. It was used alongside other measures including the St George's Respiratory Questionnaire, the Chronic Respiratory Disease Questionnaire, the Clinical COPD Questionnaire, the Hospital Anxiety and Depression score, the Medical Research Council (MRC) dyspnoea score and a range of different walking tests. Patients completed a 5-point anchor question used to assess overall response to PR from ‘I feel much better’ to ‘I feel much worse’.

Results

Data were available for 261 patients with COPD participating in seven programmes: mean (SD) age 69.0 (9.0) years, forced expiratory volume in 1 s (FEV1) 51.1 (18.7) % predicted, MRC score 3.2 (1.0). Mean change in CAT score after PR was 2.9 (5.6) points, improving by 3.8 (6.1) points in those scoring ‘much better’ (n=162), and by 1.3(4.5) in those who felt ‘a little better’ (n=88) (p=0.002). Only eight individuals reported no difference after PR and three reported feeling ‘a little worse’, so comparison with these smaller groups was not possible.

Conclusion

The CAT score is simple to implement as an outcome measure, it improves in response to PR and can distinguish categories of response.

Nocturnal monitoring of home non-invasive ventilation: the contribution of simple tools such as pulse oximetry, capnography, built-in ventilator software and autonomic markers of sleep fragmentation

Complex respiratory events, which may have a detrimental effect on both quality of sleep and control of nocturnal hypoventilation, occur during sleep in patients treated with non-invasive ventilation (NIV). Among these events are patient-ventilator asynchrony, increases in upper airway resistance (with or without increased respiratory drive) and leaks. Detection of these events is important in order to select the most appropriate ventilator settings and interface.

Simple tools can provide important information when monitoring NIV. Pulse oximetry is important to ensure that adequate oxygen saturation is provided and to detect either prolonged or short and recurrent desaturations. However, the specificity of pulse oximetry tracings during NIV is low. Transcutaneous capnography helps discriminate between hypoxaemia related to ventilation/perfusion mismatch and hypoventilation, documents correction of nocturnal hypoventilation and may detect ventilator-induced hyperventilation, a possible cause for central apnoea/hypopnoea and glottic closure. Data provided by ventilator software help the clinician by estimating ventilation, tidal volume, leaks and the rate of inspiratory or expiratory triggering by the patient, although further validation of these signals by independent studies is indicated.

Finally, autonomic markers of sympathetic tone using signals such as pulse wave amplitude of the pulse oximetry signal can provide reliable information of sleep fragmentation.

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