Cachexia in Chronic Obstructive Pulmonary Disease (COPD)

The prevalence and mortality of chronic obstructive pulmonary disease (COPD) in elderly patients are increasing worldwide. Low body mass index (BMI) is a well-known prognostic factor for COPD. Cachexia and muscle wasting is well recognized as common and partly reversible features of COPD, adversely affecting disease progression and prognosis. There is considerable heterogenicity in the rate of lung function decline in COPD, the determinants of which are largely unknown. Observational studies in COPD indicate that low BMI is associated with worse outcomes, and overweight/obesity has a protective effect - the so-called "obesity paradox". We aimed to determine the relationship between BMI and the rate of FEV1 decline. The design is a cross-sectional study, including 220 patients with stable COPD as investigated group (IG), aged 40-75 years and 58 non-COPD subjects, matched by gender, age, BMI, smoking-status, as control group (CG). All study subjects underwent pulmonary evaluation (dyspnea severity assessment, baseline and postbronchodilator spirometry, gas analyses), BMI measurement. We analyzed BMI in 4 categories: BMI-I (< 18.5 or < 20 kg/m2), BMI-II (18.5 or 20 to < 25 kg/m2), BMI-III (25 to < 29 or < 30 kg/m2) and BMI-IV (≥29 or ≥ 30 kg/m2). The analysis indicated incorrect distribution of frequencies for BMI (kg/m²) values for Shapiro-Wilk W=0.9746; p=0.00007, which is why appropriate non-parameter statistical tests were applied to the analyses. For p<0.05, no significant difference was established between the four IG subgroups in relation to the height of the BMI (Kruskal-Wallis H test: p=0.0291). Additional analysis in both groups indicated an average BMI of 25.4±3.8 kg/m² with a min/max of 17.6 /35.5 kg/m² in IG vs. 26.2±2.5 kg/m² with a min/max of 19.4 /33.2 kg/m² in CG. 50% of IG participants were less than 25.3kg/m² for Median IQR=25.3 (22.9-27.4), and in 50% of CG it was Median IQR=29.2. For p<0.05, the analysis indicated a significant association between the nutrition of subjects and the subgroup (GOLD 1→ GOLD 4) to which they belonged (Fisher Freeman Halton test: p=0.023). With decline of FEV1, BMI also declined. Analysis between the two (IG/CG) groups indicated that, for p<0.05, there is a significant association between nutrition and the group to which the respondents belong (Pearson Chi-square test: X2=8,691; df=2; p=0.0129). CG respondents were 2,648 times more frequent obese compared to IG [OR=2.65 (1.37–5.13) 95% CI]. In this review, recent insights are presented in the frequency of cachexia in COPD. In mild to moderate COPD, higher BMI was associated with a less rapid decline of FEV1 in male patients whereas this association was minimal in female patients. This gender-specific BMI effect was independent of COPD severity and smoking status. These novel findings support the obesity para�dox in COPD: compared to normal BMI, low BMI is a risk factor for accelerated lung function decline, whilst high BMI has a protective effect. The relationship may be due to common but as-of-yet unknown causative factors; further investigation into which may reveal novel endotypes or targets for therapeutic intervention

Alpha-1 antitrypsin deficiency (AATD) in a young female patient

Introduction The alpha-1 antitrypsin deficiency (AATD) is a hereditary autosomal codominant disease. The phenotype Pi ZZ is associated more frequently with pulmonary disease and is responsible for the presence of emphysema early in life, particularly in smokers. Generally, AATD is suspected in young patients with pulmonary emphysema or chronic obstructive pulmonary disease (COPD). Patients often suffer from diagnostic gaps and are misdiagnosed with chronic obstructive pulmonary disease (COPD), asthma, and airway hyper-reactivity (AHR), as AATD may present with nonspecific respiratory symptoms. AATD is most common in white people, and it most frequently affects the lungs and liver. In the lungs, the most common manifestation is early-onset (patients in their 30s and 40s) pan acinar emphysema most pronounced in the lung bases. However, diffuse or upper lobe emphysema can occur, as can bronchiectasis. The most frequently described symptoms include dyspnea, wheezing and cough. Pulmonary function testing shows findings consistent with COPD; however, bronchodilator responsiveness may be seen and may be labelled as asthma. Case presentation We describe a case of a 40-year-old Caucasian female patient, admitted to hospital because of dyspnea, malaise, cough. Symptoms started one year ago, after mild SARS-COV 2 infection. Chest X-ray during the acute illness described emphysema, with flattened diaphragm, and no signs of consolidation. According to history she was a non-smoker, office worker, with negative family history of respiratory or liver illness. She never used any regular therapy before, no comorbid diseases and denied frequent respiratory infections during childhood. Chest computer tomography (CT) presented pan acinar emphysema most pronounced in the lung bases. Post bronchodilator spirometry revealed forced expiratory volume in 1st second (FEV1) 54%, and forced vital capacity (FVC) 84%, with FEV1/FVC=0.64. Routine biochemistry laboratory was normal. Gas analyses noted respiratory failure type 1 (partial) with hypoxemia partial oxygen pressure 8.1kPa, hypocapnia because of hyperventilation with partial carbo dioxide pressure 4.1kPa, and oxygen saturation 92%. Echocardiography without any findings of right heart failure, normal systolic pulmonary arterial pressure (sPAP). Abdominal ultrasound without pathological findings, no liver disease detected. According to CT finding the patient was sent to the Institute for clinical immunology and genetic disorders where the serum value of alpha-1 antitrypsin was measured. The value was 0,2 micromoles /L (reference value 5-6 micromole /L). The patient was prescribed inhaled therapy of long acting anticholinergic, short acting beta-2 agonist. She was also suggested therapy with intravenous human alpha 1-proteinase inhibitor (AAT augmentation therapy). Conclusion It is never too late to suspect AATD, especially in a patient with an unusual medical history. In recent years, evidence is beginning to emerge that there may be value in identifying and treating patients who do not already have deterioration of functional parameters. The Alpha-1 Foundation recommendations for the diagnosis and management of AATD in adult patients indicate that treatment should be provided for patients with FEV1 between 30 and 65%. It may be useful to evaluate and treat patients based on clinical symptoms, even outside the established parameters, in particular cases

Lung cancer as a comorbidity of chronic obstructive pulmonary disease

COPD is a risk factor for lung cancer development independent of smoking status, with three to six times more likely to develop lung cancer at a rate of 0.8–1.7%/year. This may be associated with genetic susceptibility to cigarettes, chronic inflammation caused by toxic gases. Inflammatory mediators may promote the growth of bronchioalveolar stem cells, and activation of nuclear factor-κB and signal transducer and activator of transcription 3 play crucial roles in the development of lung cancer from COPD. The aim of the study is to evaluate the prevalence of lung cancer in patients with COPD. We performed a retrospective study, from 2012 to 2022, among patients with pathologically confirmed diagnosis of lung cancer, aged 40-75 years. Patients with lung cancer that had COPD diagnosed >= 10 years before lung cancer diagnosis, were investigated group. Histological subtypes of lung cancer were determined based on histopathology reports and were categorized as squamous carcinoma, adenocarcinoma, small cell lung cancer (SCLC), large cell lung cancer (LCLC; including large cell neuroendocrine carcinoma), and other histological types according to 2015 WHO classification of lung tumors. At the time of registration, sex, age, BMI, smoking status, treatment history, and symptoms, including the CAT score, were recorded. In addition, at the time of registration, spirometry was performed both before and after inhalation of a bronchodilator, and a blood test and chest CT were also performed. The GOLD criteria was used to diagnose and assign severity of COPD: patients with a postbronchodilator FEV1/FVC <0.70 were classified as having COPD; FEV1 ≥0.8 was defined as mild, 0.5≤ FEV1 <0.8 as moderate, 0.3≤ FEV1 <0.5 as severe, and FEV1 ≤0.3 as extremely severe. Patients were excluded if they presented with simultaneous or sequential second primary cancers or had a history of asthma, bronchiectasis, tuberculosis, pulmonary fibrosis, or other confounding diseases. The middle age of lung cancer diagnosis was 61.1±8.5 years. Of the total number of patients with COPD and lung cancer (260), 195 (75.0%) were male and 65 (25.0%) female. 190 (73.07%) were current smokers or ex-smokers. The histological subtypes identified were as follows: squamous carcinoma (96 [36.9%]), adenocarcinoma (115 [44.2%]), SCLC ( 26 [10.0%]), LCLC (13 [5.0%]), and other histologic types (including adenosquamous, carcinoma carcinoid tumors, sarcomatoid carcinoma; 16 [6.15%]). The proportion of squamous carcinoma was higher in smokers/ex smokers with COPD, while adenocarcinoma was more frequently observed in COPD non-smokers. Emphysema predominant phenotype was an independent prognostic risk factor for squamous carcinoma. The prevalence of COPD in lung cancer patients was 35.5%. Compared with lung cancer patients with non-COPD, those with COPD were older (P<0.001), had a lower BMI (P<0.001), and majority were male (P<0.001) and smokers (P<0.001). Annual low-dose computed tomography (LDCT) is an effective procedure for the early detection of lung cancer in high-risk patients like patients with COPD

COPD and heart rhythm disturbances: Overview of supraventricular and ventricular arrhythmias

We aimed to investigate the association between COPD and heart rhythm disturbances and their relation to the severity of airflow limitation. Cross-sectional study, including 220 patients with stable COPD as investigated group (IG), aged 40-75 years and 58 non-COPD subjects, matched by gender, age, BMI, smoking-status, as control group (CG). All study subjects underwent pulmonary evaluation, resting-ECG, 24-hour-ECG-Holter monitoring. Results presented statistically significant difference between presence of atrial fibrillation (AF) in IG 49(22.3%) vs. CG 2(3.4%) (p<0.05). There was a significant linear positive correlation between AF and GOLD stage (R=0.173;p<0.05). With decrease of FEV1(GOLD1→GOLD4), the frequency of AF increased significantly. Four ventricular rhythm disturbances were processed: bigeminy, couplets, polymorphic ectopic ventricular beats (PEVB) and un-sustained ventricular tachycardia (UVT). There was no significant association between subgroups of IG and bigeminy and IG 18(8.2%) vs. CG 4(6.9%) (p=0.25). With decrease of FEV1(GOLD1→GOLD4), the frequency of couplets increased significantly. Results presented statistically significant difference between presence of PEVB in IG 21(9.5%) vs. CG 0(0.0%) (p=0,01). The presence of UVT was not registered in GOLD1, in GOLD2 2(3.2%), GOLD 3 2(3.8%), GOLD4 2(4.1%). There was no significant association between subgroups of IG and UVT (Fisher-Freeman-Halton test:p=0.9). Results presented statistically significant difference between presence of PEVB in IG 6(2.7%) vs. CG 0(0.0%) (p=0,07). As a conclusion, there is an urgent need to develop strategies for detection and early treatment of life-threatening arrhythmias in COPD patients