Respiratory symptoms, exacerbations and sleep disturbances are more common among participants with asthma and chronic airflow limitation: an epidemiological study in Estonia, Iceland and Sweden

Background Chronic airflow limitation (CAL) is a hallmark of chronic obstructive pulmonary disease but is also present in some patients with asthma. We investigated respiratory symptoms, sleep and health status of participants with and without CAL with particular emphasis on concurrent asthma using data from adult populations in Iceland, Estonia and Sweden investigated within the Burden of Obstructive Lung Disease study.Methods All participants underwent spirometry with measurements of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) before and after bronchodilation. CAL was defined as postbronchodilator FEV1/FVC below the lower limit of normal. IgE-sensitisation and serum concentrations of eosinophil-derived neurotoxin (S-EDN) were assessed in a subsample. The participants were divided into four groups: no self-reported doctor’s diagnosed asthma or CAL, asthma without CAL, CAL without asthma and asthma and CAL: χ2 test and analysis of variance were used in bivariable analyses and logistic and linear regression when analysing the independent association between respiratory symptoms, exacerbations, sleep-related symptoms and health status towards CAL, adjusting for centre, age, sex, body mass index, smoking history and educational level.Results Among the 1918 participants, 190 (9.9%) had asthma without CAL, 127 (6.6%) had CAL without asthma and 50 (2.6%) had CAL with asthma. Having asthma with CAL was associated with symptoms such as wheeze (adjusted OR (aOR) 6.53 (95% CI 3.53 to 12.1), exacerbations (aOR 12.8 (95% CI 6.97 to 23.6), difficulties initiating sleep (aOR 2.82 (95% CI 1.45 to 5.48), nocturnal gastro-oesophageal reflux (aOR 3.98 (95% CI 1.79 to 8.82)) as well as lower physical health status. In these analyses, those with no asthma and no CAL were the reference group. The prevalence of IgE-sensitisation was highest in both asthma groups, which also had higher levels of S-EDN.Conclusion Individuals with self-reported asthma with CAL suffer from a higher burden of respiratory and sleep-related symptoms, higher exacerbation rates and lower health status when compared with participants with asthma alone or CAL alone

Factors associated with lung cancer in COPD patients

Background: The risk of dying of lung cancer is up to eightfold higher in patients with COPD than in age- and gender-matched controls. The aim of this study was to investigate the factors associated with lung cancer in a large cohort of COPD patients from primary care centers. Methods: To analyze whether age, gender, socioeconomic factors, comorbidity, and medication affect the risk of lung cancer in COPD, we used a COPD cohort of primary care patients. Data from primary care medical records and mandatory Swedish national registers were collected and linked in this population-based, retrospective observational registry study (NCT01146392). Results: Of the total cohort, 19,894 patients were included in the study. Five hundred and ninety-four lung cancer cases were diagnosed, corresponding to 3.0% of the studied population. In a multivariate analysis, the risk of lung cancer was lower if the COPD patients had a concurrent asthma diagnosis (HR: 0.54, CI: 0.41-0.71), while the risk of lung cancer increased with increasing age. A decreased lung cancer risk was observed in an exposure-dependent manner in patients who were prescribed inhaled corticosteroids (HR: 0.52, CI: 0.37-0.73), while the opposite was found for the use of acetylsalicylic acid (HR: 1.58, CI: 1.15-2.16). Conclusion: In this large population-based cohort, a concurrent asthma diagnosis and use of inhaled corticosteroids were independently related to decreased risk of lung cancer in COPD patients, while the use of acetylsalicylic acid was associated with an increased risk. The findings of the present study should be seen as hypothesis generating and need to be confirmed in prospective studies

Asthma and COPD overlap (ACO) is related to a high burden of sleep disturbance and respiratory symptoms : results from the RHINE and Swedish GA2LEN surveys

Background: The term Asthma and COPD Overlap (ACO) describes a condition where asthma and COPD overlap. We aimed to investigate associations between ACO and insomnia and respiratory symptoms, and to investigate the prevalence of ACO and the characteristics of subjects with ACO in two Northern European population studies. Methods: The study comprised 25 429 subjects aged ≥ 40 years who participated in one of two Northern European general population surveys. Both surveys included questions on asthma, COPD, respiratory and sleep-related symptoms, including difficulty initiating sleep, difficulty maintaining sleep, early-morning awakening, and excessive daytime sleepiness. ACO was defined as having both self-reported asthma and COPD. Results: The prevalence of ACO was 1.0%. The group with ACO had a higher prevalence of both insomnia and respiratory symptoms than subjects with only asthma or COPD. Having ACO was independently associated with a 2-3 times higher probability of having sleep-related symptoms as compared with the group without asthma or COPD, after adjustment for age, sex, BMI, smoking history and educational level (adjusted odds ratio 2.14-3.36, 95% CI). Conclusion: Subjects with ACO have a high prevalence of insomnia and respiratory symptoms. To our knowledge, this is the first study to assess the association between sleep-related symptoms and ACO

Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer

Background: Identification of targetable EML4-ALK fusion proteins has revolutionized the treatment of a minor subgroup of non-small cell lung cancer (NSCLC) patients. Although fluorescence in situ hybridization (FISH) is regarded as the gold standard for detection of ALK rearrangements, ALK immunohistochemistry (IHC) is often used as screening tool in clinical practice. In order to unbiasedly analyze the diagnostic impact of such a screening strategy, we compared ALK IHC with ALK FISH in three large representative Swedish NSCLC cohorts incorporating clinical parameters and gene expression data. Methods: ALK rearrangements were detected using FISH on tissue microarrays (TMAs), including tissue from 851 NSCLC patients. In parallel, ALK protein expression was detected using IHC, applying the antibody clone D5F3 with two different protocols (the FDA approved Ventana CDx assay and our in house Dako IHC protocol). Gene expression microarray data (Affymetrix) was available for 194 patients. Results: ALK rearrangements were detected in 1.7% in the complete cohort and 2.0% in the non-squamous cell carcinoma subgroup. ALK protein expression was observed in 1.9% and 1.5% when applying the Ventana assay or the in house Dako protocol, respectively. The specificity and accuracy of IHC was high (>99%), while the sensitivity was between 69% (Ventana) and 62% (in house Dako protocol). Furthermore, only 67% of the ALK IHC positive cases were positive in both IHC assays. Gene expression analysis revealed that 6/194 (3%) tumors showed high ALK gene expression (≥6AU) and of them only three were positive by either FISH or IHC. Conclusion: The overall frequency of ALK rearrangements based on FISH was lower than previously reported. The sensitivity of both IHC assays was low, and the concordance between the FISH and the IHC assays poor, questioning current strategies to screen with IHC prior to FISH or completely replace FISH by IHC

Sleep-related and respiratory symptoms (adjusted^* odds ratio (95% CI)).

<p>Sleep-related and respiratory symptoms (adjusted^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0195055#t003fn001" target="_blank">*</a>} odds ratio (95% CI)).</p

Prevalence of sleep-related symptoms in relation to asthma and COPD in men and women.

<p>(Controls: subjects with no self-reported respiratory condition, difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), early morning awakenings (EMA), excessive daytime sleepiness (EDS).</p

Prevalence of asthma, COPD and ACO in relation to age and sex.

<p>Prevalence of asthma, COPD and ACO in relation to age and sex.</p

Overlap of asthma and COPD.

<p>Overlap of asthma and COPD.</p

Sleep-related and respiratory symptoms (adjusted^* odds ratio (95% CI)) in participants with available spirometric data.

<p>Sleep-related and respiratory symptoms (adjusted^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0195055#t005fn001" target="_blank">*</a>} odds ratio (95% CI)) in participants with available spirometric data.</p