An Alpha-1 Antitrypsin Deficiency Screening Study in Patients with Chronic Obstructive Pulmonary Disease, Bronchiectasis, or Asthma in Turkey.

Purpose: Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition characterized by decreased serum alpha-1 antitrypsin (AAT) levels. We aim to identify AATD in patients with chronic obstructive pulmonary disease (COPD), bronchiectasis, or asthma and to report the frequency of AAT variants in Turkey. Patients and Methods: This non-interventional, multicenter, prospective study was conducted between October 2021 and June 2022. Adult patients with COPD, bronchiectasis, asthma, liver symptoms, or family members with AATD were included. Demographic and clinical characteristics, pulmonary diagnosis, respiratory symptoms, and AAT serum levels were assessed. Whole blood samples were collected as dried blood spots, and the most common AATD mutations were simultaneously tested by allele-specific genotyping. Results: A total of 1088 patients, mainly diagnosed with COPD (92.7%) and shortness of breath (78.7%), were assessed. Fifty-one (5%) were found to have AATD mutations. Fifteen (29.4%) patients had Pi*S or Pi*Z mutations, whereas 36 (70.6%) patients carried rare alleles Pi*M malton (n=18, 35.3% of mutations), Pi*I (n=8, 16%), Pi*P lowell (n=7, 14%), Pi*M heerlen (n=2, 4%), and Pi*S iiyama (n=1, 2%). The most common heterozygous combinations were Pi*M/Z (n=12, 24%), and Pi*M/M malton (n=11, 22%). Ten patients with severe AATD due to two deficiency alleles were identified, two with the Pi*Z/Z genotype, four with the genotype Pi*M malton/M malton, three with Pi*Z/M malton, and one with Pi*Z/M heerlen. Conclusion: Our results identified AATD mutations as a genetic-based contributor to lung disease in patients with COPD or bronchiectasis and assessed their frequency in a population of Turkish patients.

Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is characterized by diagnosis at an advanced stage, low rate of operability and poor survival. Therefore, there is a need for a biomarker in NSCLC patients to predict the likely outcome and to accurately stratify the patients in terms of the most appropriate treatment modality. To evaluate prognostic value of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in NSCLC. A total of 124 NSCLC patients (mean ± standard deviation age: 60.7 ± 9.3 years, 94.4% were males) were included in this retrospective study. Data were retrieved from the hospital records. The association of NLR and PLR with clinicopathological factors and overall survival was analyzed. One-year, 2-year and 5-year survival rates were 59.2%, 32.0%, and 16.2%, respectively. Median duration of survival was shorter in patient groups with elevated NLR and PLR. Five-year survival rate was quite lower in patient groups with elevated NLR and PLR. Hazard rate (HR) for mortality was 1.76 (95% confidence interval [CI]: 1.19-2.61, P = .005) for NLR ≥ 3 over NLR < 3. HR was 1.64 (95%CI: 1.11-2.42, P = .013) for PLR ≥ 150 over PLR < 150. Cox-regression analysis revealed that, when adjusted for other independent predictors of survival, NLR and PLR still remain significant predictors of poorer survival. Our findings indicate that elevated pretreatment NLR and PLR are associated with advanced disease and poor survival in NSCLC patients, NLR and PLR values are correlated with each other.

Fatigue has a prominent impact on health lasting 12-weeks after COVID-19 infection.

Background: While the amount of information on many issues related to COVID-19 has increased, the long-term consequences of illness and disability remain largely unclear. In previous studies on COVID-19 infections, long-lasting functional and symptomatic abnormalities have also been shown. It is predicted that survivors of COVID-19 may have to deal with physical or psychological problems later. Aim: We aimed to evaluate long-lasting symptoms including fatigue and investigate the associated risk factors. Methods: In this prospective cohort study, 132 consecutive COVID-19 patients who were previously diagnosed and admitted 13±1 weeks after diagnosis were included. The Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale, the Beck Anxiety Inventory, the Beck Depression Inventory, and the Lawton Instrumental Activities of Daily Living (IADL) Scale were applied in the follow-up visit. Results: The median age of the patients (76 male, 56 female) was 52. Eighty (61%) of the patients were hospitalized, while 52 (39%) of them were not hospitalized. At least one symptom persisted in 103 (78%) patients, with fatigue (n=48, 36%) being the most common symptom. Both dyspnea and fatigue were more prominent in women than in men (34% vs. 11%, p=0.001 and 46% vs 29%, p=0.03; respectively). Persisted symptoms including fatigue were not significantly associated with hospitalization status. The FACIT scores of the patients at 12 weeks were positively associated with their depression and anxiety levels (R: 0.55, p=0.0001 and R: 0.42, p=0.0001), while they were negatively associated with their IADL scores (R: -0.25, p=0.004). Conclusions: Fatigue was the most frequent persistent symptom. The initial fatigue scores were higher in the severely ill patients. Persistent fatigue was not associated with disease severity but was closely associated with anxiety and depression.

The CO-MIND Study: Chronic Obstructive Pulmonary Disease Management in Daily Practice and Its Implications for Improved Outcomes According to GOLD 2019 Perspective.

Purpose: GOLD 2019 proposed a novel treatment decision tool for follow-up based on the predominant trait (exacerbation or dyspnea) of patients, alongside treatment escalation and de-escalation strategies. This study was designed to provide an up-to-date snapshot of patient and disease characteristics, treatment pathways, and healthcare resource use (HRU) in COPD in real life, and comprehensively examine patients considering GOLD 2019 recommendations. Patients and Methods: This mixed design, observational, multicenter (14 pulmonology clinics) study included all patients with a documented COPD diagnosis (excluding asthma-COPD overlap [ACO]) for ≥12 months, aged ≥40 years at diagnosis who had a COPD-related hospital visit, spirometry test and blood eosinophil count (BEC) measurement under stable conditions within the 12 months before enrollment between February and December 2020. Data were collected cross-sectionally from patients and retrospectively from hospital medical records. Results: This study included 522 patients (GOLD group A: 17.2%, B: 46.4%, C: 3.3%, D: 33.1%), of whom 79.5% were highly symptomatic and 36.2% had high risk of exacerbation. Exacerbations (n = 832; 46.6% moderate, 25.5% severe) were experienced by 57.5% of patients in the previous 12 months. Inter-rater agreement between investigators and patients regarding the reason for visit was low (κ coefficient: 0.338, p = 0.001). Inhaled treatment was modified in 88 patients at index, mainly due to symptomatic state (31.8%) and exacerbations (27.3%); treatment was escalated (57.9%, mainly switched to LABA+LAMA+ICS), inhaler device and/or active ingredient was changed (36.4%) or treatment was de-escalated (5.7%). 27% had ≥1 hospital overnight stay over 12 months. Emergency department visits and days with limitation of daily activities were higher in group D (p < 0.001). Conclusion: Despite being on-treatment, many patients with COPD experience persistent symptoms and exacerbations requiring hospital-related HRU. A treatable trait approach and holistic disease management may improve outcomes by deciding the right treatment for the right patient at the right time.

A 34-Year-Old male admitted with pulmonary tuberculosis complicated by hydropneumothorax and mediastinal emphysema.

Spontaneous hydropneumothorax (HP) and mediastinal emphysema (ME) are infrequently presented complications of pulmonary tuberculosis (TB). A-34-year-old Pakistani male presented with dyspnea, productive cough, and right-sided pleuritic chest pain. He had no history of any surgery, TB, comorbid disease, or other serious pulmonary diseases. Chest radiography revealed a right-sided HP and parenchymal infiltration. The laboratory results of pleural effusion showed elevated adenosine deaminase levels with the empyema features. Acid-fast bacilli were detected and Mycobacterium tuberculosis without any drug resistance grew in the culture both in the sputum and pleural fluid. A chest tube was inserted immediately. A prolonged airway leak was detected. Hepatotoxicity protocol has been initialized (due to increased hepatic enzymes in the initial presentation) and followed without observing any complications associated with the treatment. On the 25th day of the standard TB treatment protocol, we observed hepatic enzymes in the normal range. Around 40-days of a hospitalization period, he started developing fever and methicillin-resistant Staphylococcus aureus was detected in the pleural fluid culture. We introduced linezolid to the treatment regimen in addition to the antituberculosis protocol. Although spontaneous ME is a benign disease, it might be life-threatening and difficult to manage when complicated with HP and active TB infection. Active TB should be considered a differential diagnosis once ME or HP was detected, and treatment should be started immediately for both diseases.

Does smoking impair sleep hygiene?

BACKGROUND: Sleep architecture and sleep hygiene might be disrupted by several pathogenetic mechanisms, and the effect of smoking has not been evaluated. OBJECTIVE: To investigate the effect of smoking on sleep hygiene behaviors that might be associated with the deterioration of quality-of-life (QoL) parameters. METHODS: In a prospective cross-sectional study, smokers (n=114) and nonsmokers (n=119) were included. The Pittsburgh Sleep Quality Index (PSQI), the Epworth Daytime Sleepiness Scale (ESS), the Sleep Hygiene Index (SHI), and the Short Form-36 quality of life scale (SF-36) were applied. RESULTS: We found that none of the components, as well as the PSQI total score were affected in smokers compared with the nonsmoker controls (65.5% of smokers had poor sleep compared to 62.5% of nonsmokers). Although smokers tend to get out of bed at different times from day to day and do important work before bedtime (components of the SHI) more often than non-smokers, no significant differences were detected between groups in any component and SHI total score (27.91±6.72 for smokers and 29.23±8.0 for non-smokers). ESS, depression and anxiety symptoms, and SHI scores in smokers with poor sleep quality were significantly different compared with smokers that had normal sleep quality. Both PSQI and SHI scores were inversely associated with QoL parameters. CONCLUSIONS: Our results suggest that smoking by itself is not associated with poor sleep hygiene or sleep quality. It can be concluded that worse SHI and quality of sleep negatively affect QoL, depression, and anxiety in smokers.

Does smoking impair sleep hygiene? / O tabagismo prejudica a higiene do sono?

ABSTRACT Background: Sleep architecture and sleep hygiene might be disrupted by several pathogenetic mechanisms, and the effect of smoking has not been evaluated. Objective: To investigate the effect of smoking on sleep hygiene behaviors that might be associated with the deterioration of quality-of-life (QoL) parameters. Methods: In a prospective cross-sectional study, smokers (n=114) and nonsmokers (n=119) were included. The Pittsburgh Sleep Quality İndex (PSQI), the Epworth Daytime Sleepiness Scale (ESS), the Sleep Hygiene Index (SHI), and the Short Form-36 quality of life scale (SF-36) were applied. Results: We found that none of the components, as well as the PSQI total score were affected in smokers compared with the nonsmoker controls (65.5% of smokers had poor sleep compared to 62.5% of nonsmokers). Although smokers tend to get out of bed at different times from day to day and do important work before bedtime (components of the SHI) more often than non-smokers, no significant differences were detected between groups in any component and SHI total score (27.91±6.72 for smokers and 29.23±8.0 for non-smokers). ESS, depression and anxiety symptoms, and SHI scores in smokers with poor sleep quality were significantly different compared with smokers that had normal sleep quality. Both PSQI and SHI scores were inversely associated with QoL parameters. Conclusions: Our results suggest that smoking by itself is not associated with poor sleep hygiene or sleep quality. It can be concluded that worse SHI and quality of sleep negatively affect QoL, depression, and anxiety in smokers.

RESUMO Antecedentes: A arquitetura e a higiene do sono podem ser interrompidas por vários mecanismos patogenéticos, e o efeito do tabagismo ainda não foi avaliado. Objetivo: Investigar o efeito do tabagismo nos comportamentos de higiene do sono que podem estar associados à deterioração dos parâmetros de qualidade de vida (QV). Métodos: Em um estudo transversal prospectivo, foram incluídos fumantes (n=114) e não fumantes (n=119). Foram aplicados o índice de qualidade do sono de Pittsburgh (Pittsburgh Sleep Quality İndex - PSQI), a escala de sonolência diurna de Epworth (ESS), o índice de higiene do sono (Sleep Hygiene Index - SHI) e a escala de qualidade de vida Short Form-36 (SF-36). Resultados: Descobrimos que nenhum dos componentes, assim como o escore total do PSQI, foram afetados em fumantes em comparação com os controles não fumantes (65,5% dos fumantes dormiam mal em comparação com 62,5% dos não fumantes). Embora os fumantes tendam a sair da cama em horários diferentes do dia a dia e fazer trabalhos importantes antes de dormir (componentes do SHI) com mais frequência do que os não fumantes, não foram detectadas diferenças significativas entre os grupos em qualquer componente e pontuação total do SHI (27,91±6,72 para fumantes e 29,23±8,0 para não fumantes). A ESS, os sintomas de depressão e ansiedade e os escores SHI em fumantes com má qualidade de sono foram significativamente diferentes em comparação com fumantes com qualidade de sono normal. Os escores do PSQI e SHI foram inversamente associados aos parâmetros de QV. Conclusões: Nossos resultados sugerem que o tabagismo por si só não está associado à má higiene ou qualidade do sono. Pode-se concluir que o pior SHI e a qualidade do sono afetam negativamente a QV, a depressão e a ansiedade em fumantes.

The Effect of Sleep Hygiene and Sleep Deterioration on Quality of Life in Shiftworking Healthcare Professionals.

INTRODUCTION: Deterioration in sleep quality and sleep hygiene may result in impairments on mental and physical health leading to deterioration of quality of life (QoL) in healthcare shift workers. We aimed to determine the presence of sleep deterioration as well as poor sleep hygiene, and if any, the effects of these on health-related outcomes. METHODS: This study prospectively included healthcare professionals who did and did not work shifts (n=90 and n=66, respectively). The participants completed the Pittsburgh Sleep Quality Index (PSQI), Sleep Hygiene Index (SHI), Epworth Daytime Sleepiness Scale (EDSS), Short Form-36 quality of life scale (SF-36), and the Beck depression (BD) and Beck anxiety (BA) scales. RESULTS: Although the total PSQI scores showed a tendency to increase in shift workers, no significant differences were observed in total scores as well as subdivisions, except for an increase in sleep latency. Increased SHI total score in shift workers were represent more deteriorated sleep hygiene behavior (p=0.002). Increased needs of daytime nap, variability of both go and get out of bed and stay in bed longer than usual were recorded respectively (p: 0.001, p: 0.001, p: 0.001, p: 0.001, p: 0.001). SHI had prominent effects on QoL parameters such as vitality (r=-0.284, p=0.007), social function (r=-0.323, p=0.002), mental health (r=-0.274, p=0.009), and calculated mental component total score (r=-0.302, p=0.004). CONCLUSION: In our study, we clearly detected prolonged sleep latency and poor sleep hygiene in shift workers which should be responsible for the deterioration of QoL.

D-dimer/Fibrinogen ratio and recurrent exacerbations might have a potential impact to predict 90-day mortality in patients with COPD exacerbation.

Background: According to the World Health Organisation reports (WHO), COPD is the third leading cause of overall in the World by 2020. Aim: We aimed to determine the prognostic predictors of 90-day mortality after an initial exacerbation in patients with acute exacerbation of COPD (AECOPD). Results: Increased Charlson Comorbidity Score(CCS) (HR:1.47; p<0.05), readmission after initial exacerbation (HR:1.47; p<0.05) were predictive risk factors for 30-day mortality in multivariable regression model. The 90-day mortality rate was %11.8. Hypertension, increased median age, nutrition risk score (NRS), CCS, CAT score, and mMRC 4th level were possible risk factors for 90-day mortality. There was a significant difference in the mortality of patients with D-dimer/Fibrinogen ratios>0.11 and ≤0.11 (HR:2.47; p<0.05). Recurrent exacerbations after discharge were predictive risk factors for 90-day mortality in the multivariable regression model (HR:2.25; p<0.001) with the increased mortality risk 4.73 times (HR:4.73; p=0.002). Furthermore, a 1-unit increment of acute exacerbation increased the mortality risk 3.39 times (HR:3.39; p<0.001). Conclusion: Our study showed that D-dimer/Fibrinogen ratio but not D-dimer and recurrent exacerbations after discharge might have a critical impact on 90-day mortality.

The role of typical and atypical pathogens in acute exacerbations of chronic obstructive pulmonary disease.

OBJECTIVES: The exact role of Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila in the development of chronic obstructive pulmonary disease exacerbations remains to be elucidated. This study was conducted to identify nonspecific and atypical pathogens associated with acute exacerbations of COPD. MATERIALS AND METHODS: Between February 2013 and February 2015, 107 patients were analyzed. Sixty-nine comprised the inpatient and 38 comprised the outpatient treatment group. RESULTS: When nonspecific culture results were taken into consideration only a causative organism could be detected in 46.7% of the patients. The detection rate increased to 85.1% with the additional use of polymerase chain reaction (PCR), direct fluorescent antibody (DFA) test, and culture methods. More than one causative agent was responsible for COPD exacerbation in 53.3% of patients: two agents in 37.3%, three agents in 15%, and four agents in 0.9%. H. influenzae was detected in 63 (58.9%) patients, S. pneumoniae in 57 (53.2%), P. aeruginosa in 15 (14.0%), and L. pneumophila in 11 (10%). L. pneumophila was the more commonly isolated agent in the inpatient group (P = 0.002). Patients receiving continuous oxygen therapy and noninvasive mechanical ventilation were more likely to have an exacerbation associated with P. aeruginosa (P = 0.008 and P = 0.009, respectively). CONCLUSION: The additional use of DFA for Legionella and multiplex PCR in combination with nonspecific microbiological culturing methods greatly improves the ability to identify infectious agents in acute exacerbations of COPD. There should be a high index of suspicion for P.aeruginosa as a causative organism, particularly in subjects receiving continuous oxygen therapy and/or using NIV and L. pneumophila should certainly be taken into consideration in severe COPD exacerbations.

Bronchodilator efficacy of tiotropium/formoterol (18/12 µg once daily via a Discair inhaler), tiotropium alone (18 µg by Handihaler) or combined with formoterol (12 µg twice daily by Aerolizer) in adults with moderate-to-severe stable COPD.

Objectives: The bronchodilator efficacy of a once-daily fixed-dose combination of tiotropium/formoterol (18/12 µg administered via a dry-powder inhaler, Discair) [TIO/FORMfixed group] vs a single-dose of tiotropium (18 µg) by Handihaler1 alone [TIOmono group], or combined with formoterol 12 µg twice-daily by Aerolizer2 [TIO/FORMbid group] was compared in patients with moderate-to-severe stable COPD.Methods: COPD patients were randomized (28 patients/group) to receive TIO/FORMfixed, TIOmono, or TIO/FORMbid. AUC for the changes in FEV1 and FVC over a 24-h period; bronchodilator response (100 ml improvement in FEV1) in the first 30 min; maximum changes in FEV1 and FVC; and safety data were recorded. The primary endpoint was to confirm the non-inferiority of TIO/FORMfixed vs TIO/FORMbid in terms of the AUC for the changes in FEV1 over a 24-h period.Results: Changes in AUC0-24h for FEV1 and FVC were similar for TIO/FORMfixed and TIO/FORMbid, and were superior to TIOmono (p < 0.001). A positive bronchodilator response at 30 min was demonstrated in 50%, 64%, and 71% of patients in the TIOmono, TIO/FORMbid, and TIO/FORMfixed groups, respectively (NS). Maximum FEV1 and FVC changes were measured as 0.25/0.41 L, 0.32/0.49 L, and 0.37/0.53 L, for TIOmono, TIO/FORMbid, and TIO/FORMfixed, respectively (FEV1: TIO/FORMfixed vs TIOmono, p = 0.0017 and TIO/FORMfixed vs TIO/FORMbid, p = 0.4846); no differences were recorded between the combination groups.Conclusions: The 24-h bronchodilator efficacy of TIO/FORMfixed 18/12 µg once-daily by Discair3 was non-inferior to a combination of tiotropium 18 µg by Handihaler plus formoterol 12 µg twice-daily by Aerolizer, and superior to tiotropium 18 µg monotherapy by Handihaler.