COVID-19 and liver injury: An ongoing challenge.

The new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019, in Wuhan, China. The virus was rapidly spread worldwide, causing coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is presented, usually, with typical respiratory symptoms (i.e., dyspnea, cough) and fever, extrapulmonary manifestations are also encountered. Liver injury is a common feature in patients with COVID-19 and ranges from mild and temporary elevation of liver enzymes to severe liver injury and, even, acute liver failure. The pathogenesis of liver damage is not clearly defined; multiple mechanisms contribute to liver disorder, including direct cytopathic viral effect, cytokine storm and immune-mediated hepatitis, hypoxic injury, and drug-induced liver toxicity. Patients with underlying chronic liver disease (i.e., cirrhosis, non-alcoholic fatty liver disease, alcohol-related liver disease, hepatocellular carcinoma, etc.) may have greater risk to develop both severe COVID-19 and further liver deterioration, and, as a consequence, certain issues should be considered during disease management. The aim of this review is to present the prevalence, clinical manifestation and pathophysiological mechanisms of liver injury in patients with SARS-CoV-2 infection. Moreover, we overview the association between chronic liver disease and SARS-CoV-2 infection and we briefly discuss the management of liver injury during COVID-19.

Real-world safety and efficacy data of immunotherapy in patients with cancer and autoimmune disease: the experience of the Hellenic Cooperative Oncology Group.

BACKGROUND: Data on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with concurrent autoimmune diseases (AID) are limited. METHODS: We performed a retrospective multicenter review of medical records of patients with cancer and underlying AID who received ICI. The primary endpoint was progression-free survival (PFS). RESULTS: Among 123 patients with pre-existing AID who received ICI, the majority had been diagnosed with non-small cell lung cancer (NSCLC, 68.3%) and melanoma (14.6%). Most patients had a rheumatologic (43.9%), or an endocrine disorder (21.1%). Overall, 74 (60.2%) patients experienced an immune-related adverse event (irAE) after ICI initiation, AID flare (25.2%), or new irAE (35%). Frequent irAEs included thyroiditis, dermatitis and colitis. ICI was permanently discontinued due to unacceptable (8.1%) or fatal (0.8%) toxicity. In patients with NSCLC, corticosteroid treatment at the initiation of immunotherapy was associated with poor PFS (HR = 2.78, 95% CI 1.40-5.50, p = 0.003). The occurrence of irAE was associated with increased PFS (HR = 0.48, 95% CI 0.25-0.92, p = 0.026). Both parameters maintained their independent prognostic significance. CONCLUSIONS: ICI in patients with cancer and pre-existing AID is associated with manageable toxicity that infrequently requires treatment discontinuation. However, since severe AID flare might occur, expected ICI efficacy and toxicity must be balanced. CLINICAL TRIAL IDENTIFIER: NCT04805099.

An Observational Study to Assess the Molecular Epidemiology and Direct Medical Costs of Epidermal Growth Factor Receptor (EGFR) Mutations in Patients with Advanced EGFR Mutation-Positive Non-Small Cell Lung Cancer Treated with Afatinib in Real-World Clinical Settings in Greece.

PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line option for patients with advanced, EGFR-mutant non-small cell lung cancer (NSCLC). Afatinib, a second-generation irreversible EGFR-TKI, has been extensively used in Greece in this setting; however, real-world data regarding molecular epidemiology and financial implications of afatinib use are lacking. MATERIALS AND METHODS: This was an observational, non-interventional, multicenter, retrospective cohort study, based on real-world data collected from the medical charts/records of patients treated with afatinib between 15/03/2015 and 25/06/2020 and were recorded on a web-based data capture system. Cox models were used to assess the prognostic significance of clinicopathological parameters with respect to clinical outcomes of interest. Cost analysis was conducted from a public third-payer perspective, and only direct medical costs reimbursed by the payer were considered. RESULTS: A total of 59 patients were treated with afatinib for their EGFR mutation-positive advanced NSCLC; the median age was 61 years (range: 37-91). Performance status was zero in 61%, and brain metastases were present in 13.6%. Forty-four patients (74.6%) had a deletion in exon 19 only, while nine (15.3%) had a mutation in exon 21, 8 of them in L858R and one in L861Q. At a median follow-up of 41.8 months (95% CI 35.9-51.4), the median PFS was 14.3 months (95% CI 12.2-16.4), and the median OS was 29 months (95% CI 25.6-33.4). Corresponding values for patients with deletion 19 only were 14.3 months (95% CI 11.5-18.5) and 28.1 months (95% CI 21.1-32.6), respectively. The mean expenditure for the treatment of each patient equals €25,333.68; with €21,865.06 being attributed to drug acquisition costs, €3325.35 to monitoring costs and €143.27 to adverse event treatment-related costs. CONCLUSION: Long-term data in the real-world setting in Greece confirm activity, tolerability and cost-effectiveness of afatinib as first-line treatment of patients with advanced EGFR-mutant NSCLC. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT04640870.

Underdiagnosis, false diagnosis and treatment of COPD in a selected population in Northern Greece.

BACKGROUND: In the primary care setting, diagnosis and treatment of COPD is not always consistent with GOLD guidelines. OBJECTIVES: To calculate the prevalence of COPD underdiagnosis, false diagnosis and treatment in the general population of northern Greece. METHODS: Observational study in the context of an early COPD detection and smoking cessation project. Inclusion criteria: >40-year-old, current and former smokers (>10 pack-years) in five primary care centres of northern Greece from 2012 to 2019. Participation was achieved via a campaign (posters and advertisements in the mass media). RESULTS: We examined 5,226 subjects (mean age: 58.2 ± 12.7 years, 61.5% males, current smokers: 56.2%) of whom 564 (10.8%) had symptoms and spirometrically confirmed COPD. There were 5 groups of 'interest:' a) 117/264 (44.3%) with a previous correct diagnosis COPD and correct treatment; b) 139/264 (52.7%) previous correct diagnosis COPD but overtreatment; c) 8/264 (3%) previous correct diagnosis COPD but undertreatment; d) 461 subjects (63.6% of those with previous COPD diagnosis) had previous false diagnosis of COPD (= also overtreatment); e) 300/564 (53.2%) previously not diagnosed COPD (=underdiagnosis and also undertreatment). We found that 322/461 (69.8%) of those with a previous false diagnosis have been prescribed long-acting bronchodilators plus ICS. CONCLUSION: Among the general population subjects in northern Greece, more than 50% of patients with COPD were underdiagnosed, more than 50% of correctly diagnosed COPD patients were overtreated and most patients taking inhaled drugs were those with a false diagnosis of COPD (possibly GOLD stage 0).

Bacteriology, antibiotic resistance and risk stratification of patients with culture-positive, community-acquired pleural infection.

BACKGROUND: Community-acquired pleural infection (CAPI) is a growing health problem worldwide. Although most CAPI patients recover with antibiotics and pleural drainage, 20% require surgical intervention. The use of inappropriate antibiotics is a common cause of treatment failure. Awareness of the common causative bacteria along with their patterns of antibiotic resistance is critical in the selection of antibiotics in CAPI-patients. This study aimed to define CAPI bacteriology from the positive pleural fluid cultures, determine effective antibiotic regimens and investigate for associations between clinical features and risk for death or antibiotic-resistance, in order to advocate with more invasive techniques in the optimal timing. METHODS: We examined 158 patients with culture positive, CAPI collected both retrospectively (2012-2013) and prospectively (2014-2018). Culture-positive, CAPI patients hospitalized in six tertiary hospitals in Greece were prospectively recruited (N=113). Bacteriological data from retrospectively detected patients were also used (N=45). Logistic regression analysis was performed to identify clinical features related to mortality, presence of certain bacteria and antibiotic resistance. RESULTS: Streptococci, especially the non-pneumococcal ones, were the most common bacteria among the isolates, which were mostly sensitive to commonly used antibiotic combinations. RAPID score (i.e., clinical score for the stratification of mortality risk in patients with pleural infection; parameters: renal, age, purulence, infection source, and dietary factors), diabetes and CRP were independent predictors of mortality while several patient co-morbidities (e.g., diabetes, malignancy, chronic renal failure, etc.) were related to the presence of certain bacteria or antibiotic resistance. CONCLUSIONS: The dominance of streptococci among pleural fluid isolates from culture-positive, CAPI patients was demonstrated. Common antibiotic regimens were found highly effective in CAPI treatment. The predictive strength of RAPID score for CAPI mortality was confirmed while additional risk factors for mortality and antibiotic resistance were detected.

Acute effects of e-cigarette vaping on pulmonary function and airway inflammation in healthy individuals and in patients with asthma.

BACKGROUND AND OBJECTIVE: The acute effects of e-cigarettes have not been scientifically demonstrated yet. The aim of this study was to assess the acute changes in pulmonary function and airway inflammation in patients with asthma after vaping one e-cigarette. METHODS: Twenty-five smokers suffering from stable moderate asthma according to GINA guidelines with no other comorbidities and 25 healthy smokers matched with the baseline characteristics of the asthmatic patients were recruited. PFT, IOS, FeNO and EBC were performed before and after vaping one e-cigarette with nicotine. pH and concentrations of IL-1ß, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17A, TNF-α, ISO8 and LTB4 were measured in EBC. RESULTS: FFEV1/FVC ratio and PEF were reduced in asthmatic patients after e-cigarette. Z5Hz and R5Hz, R10Hz and R20Hz increased in both groups. FeNO and EBC pH increased by 3.60 ppb (P = 0.001) and 0.15 (P = 0.014) in asthmatic patients after e-cigarette, whereas they decreased in control group by 3.28 ppb (P < 0.001) and 0.12 (P = 0.064), respectively. The concentrations of IL-10, TNF-α and ISO8 in EBC increased in asthmatic patients after e-cigarette and the changes in concentrations of IL-1ß and IL-4 differed significantly between the two groups. CONCLUSION: E-cigarette vaping resulted in acute alteration of both pulmonary function and airway inflammation in stable moderate asthmatic patients.

The Role of Immunotherapy in Extensive Stage Small-Cell Lung Cancer: A Review of the Literature.

Lung cancer is the second most common cancer in both sexes worldwide. Small-cell lung cancer (SCLC) is a form of neuroendocrine tumor, which is classified into limited and extensive-stage disease and shows excellent initial response to chemotherapy; however, almost all patients relapse later. During the past few years, several clinical trials have evaluated the effect of addition of immunotherapy to conventional chemotherapy in patients with extensive SCLC. Checkpoint inhibitors are currently under investigation, especially the CTLA-4 and PD-1/PD-L1 inhibitors. Nowadays, evidence show a statistically significant survival benefit of adding atezolizumab, an IgG1 monoclonal antibody targeting against PD-L1, to platinum-based chemotherapy plus etoposide in patients who have not received any previous systemic therapy. Furthermore, the role of nivolumab, an IgG4 anti-PD-1 monoclonal antibody, is significant for the treatment of relapsed SCLC cases. Recently, pembrolizumab was the first immunotherapeutic agent to be approved by the FDA for patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy and at least one other prior line of chemotherapy. Nevertheless, prognostic biomarkers to immunotherapy response remain to be discovered.

Endocrine paraneoplastic syndromes in lung cancer.

Paraneoplastic syndromes are defined as a combination of clinical disorders associated with malignant diseases that are caused by the secretion of various substances by the tumor without, however, being caused by the direct growth and infiltration of the primary tumor, or due to the development of distant metastases. Despite the fact that lung cancer represents the number one cause of death from cancer worldwide, the new methods of treatment increase patient survival and the incidence of paraneoplastic syndromes. The most important ones of these are humoral hypercalcemia of malignancy, syndrome of inappropriate antidiuretic hormone, hyponatremia of malignancy, ectopic Cushing's syndrome, carcinoid syndrome, and hypoglycemia and are usually a poor prognostic marker. Early diagnosis of those syndromes is achieved using specific criteria and may lead to early diagnosis of the underlying malignancy. It is essential to treat them with the overriding objective of improving the patients' quality of life.

Chronic obstructive pulmonary disease in patients with lung cancer: prevalence, impact and management challenges.

Chronic obstructive pulmonary disease (COPD) and lung cancer share a common etiological factor (cigarette smoking) and usually coexist in everyday clinical practice. The prevalence of COPD among newly diagnosed patients with lung cancer sometimes exceeds 50%. COPD is an independent risk factor (2-4 times higher than non-COPD subjects) for lung cancer development. The presence of emphysema in addition to other factors (e.g., smoking history, age) could be incorporated into risk scores in order to define the most appropriate target group for lung cancer screening using low-dose computed tomography. Clinical management of patients with coexistence of COPD and lung cancer requires a multidisciplinary oncology board that includes a pulmonologist. Detailed evaluation (lung function tests, cardiopulmonary exercise test) and management (inhaled drugs, smoking cessation, pulmonary rehabilitation) of COPD should be taken into account for lung cancer treatment (surgical approach, radiotherapy).

Comparison of Three Screening Questionnaires for Chronic Obstructive Pulmonary Disease in the Primary Care.

BACKGROUND: Even though the diagnosis of chronic obstructive pulmonary disease (COPD) is easy and based mainly on spirometry and symptoms, the prevalence of underdiagnosis is extremely high. The use of simple screening tools (e.g., questionnaires, hand-held spirometers) has been proved to be a simple method for case finding of COPD. Nevertheless the most appropriate target group of the general population has not been specified yet. OBJECTIVES: The aim of the present study was to compare 3 screening questionnaires among smokers aged >40 years in the primary care setting. METHODS: We excluded all subjects with a previous medical diagnosis of bronchial asthma or chronic pulmonary disease other than COPD. All participants were in a stable clinical condition, filled in the International Primary Care Airways Group (IPAG) questionnaire, the COPD Population Screener (COPD-PS) questionnaire, and the Lung Function Questionnaire (LFQ) and underwent spirometry. Medical diagnosis of COPD was established by an experienced pulmonologist. RESULTS: We studied 3,234 subjects during a 3.5-year period. COPD prevalence was 10.9% (52.1% underdiagnosis). All 3 questionnaires showed extremely high negative predictive values (94-96%), so in this case the diagnosis of COPD could be safely excluded. The area under the curve was similar across the 3 questionnaires (AUCROC: 0.794-0.809). The COPD-PS questionnaire demonstrated the highest positive predictive value (41%) compared to the other 2. On the other hand, the IPAG questionnaire and LFQ demonstrated higher sensitivities than COPD-PS resulting in lower percentages of missed cases. CONCLUSIONS: Three validated screening questionnaires for COPD demonstrated different diagnostic characteristics.

Mast cells mediate malignant pleural effusion formation.

Mast cells (MCs) have been identified in various tumors; however, the role of these cells in tumorigenesis remains controversial. Here, we quantified MCs in human and murine malignant pleural effusions (MPEs) and evaluated the fate and function of these cells in MPE development. Evaluation of murine MPE-competent lung and colon adenocarcinomas revealed that these tumors actively attract and subsequently degranulate MCs in the pleural space by elaborating CCL2 and osteopontin. MCs were required for effusion development, as MPEs did not form in mice lacking MCs, and pleural infusion of MCs with MPE-incompetent cells promoted MPE formation. Once homed to the pleural space, MCs released tryptase AB1 and IL-1ß, which in turn induced pleural vasculature leakiness and triggered NF-κB activation in pleural tumor cells, thereby fostering pleural fluid accumulation and tumor growth. Evaluation of human effusions revealed that MCs are elevated in MPEs compared with benign effusions. Moreover, MC abundance correlated with MPE formation in a human cancer cell-induced effusion model. Treatment of mice with the c-KIT inhibitor imatinib mesylate limited effusion precipitation by mouse and human adenocarcinoma cells. Together, the results of this study indicate that MCs are required for MPE formation and suggest that MC-dependent effusion formation is therapeutically addressable.

Umeclidinium bromide/vilanterol combination in the treatment of chronic obstructive pulmonary disease: a review.

Chronic obstructive pulmonary disease (COPD) is a common disease among the elderly that could be prevented by smoking cessation. As it is characterized by airflow limitation that is not fully reversible, bronchodilator therapy is the first choice of treatment. Symptomatic COPD patients with or without risk for future exacerbations have a strong indication for the permanent use of long- and ultralong-acting ß2-agonists and/or long-acting muscarinic antagonists. Combining bronchodilators is an effective approach, as they demonstrate synergic action at a cellular level and have additive clinical benefits and fewer adverse events compared with increased doses of the monocomponents. Novel fixed-dose combinations of long-acting ß2-agonists/long-acting muscarinic antagonists in one inhaler have been approved for clinical use by the US Food and Drug Administration and the European Medicines Agency. This review focuses on published clinical trials about the fixed-dose combination of umeclidinium/vilanterol trifenatate in patients with COPD. Results from six studies (five of them of 12 weeks' duration and one that lasted 1 year, including more than 6,000 patients in total) showed that umeclidinium/vilanterol trifenatate improved lung function, dyspnea, and health-related quality of life and decreased the exacerbation rate with no serious adverse events. More longstanding trials are needed to evaluate the effect of the drug on disease progression and compare it directly with other fixed-dose combinations.

Smoking among adolescents in Northern Greece: a large cross-sectional study about risk and preventive factors.

BACKGROUND: The aim of the present study was to investigate epidemiological data about cigarette smoking in relation with risk and preventive factors among Greek adolescents. METHODS: We randomly selected 10% of the whole number of schools in Northern Greece (133 schools, 18,904 participants were included). Two anonymous questionnaires (smoker's and non-smoker's) were both distributed to all students so they selected and filled in only one. A parental signed informed consent was obtained using an informative leaflet about adolescent smoking. RESULTS: The main findings of the study were: a) 14.2% of the adolescents (mean age+/-SD: 15.3+/-1.7 years) reported regular smoking (24.1% in the age group 16-18 years), b) 84.2% of the current smokers reported daily use, c) students who live in urban and semirural areas smoke more frequently than those in rural areas, d) students in technically oriented schools smoke twice as frequent compared to those in general education, e) risk factors for smoking: male gender, low educational level of parents, friends who smoke (OR: 10.01, 95%CI: 8.53-11.74, p<0.001), frequent visits to internet cafes (OR:1.53, 95%CI: 1.35-1.74, p<0.001), parents, siblings (OR:2.24, 95%CI: 1.99-2.51, p<0.001) and favorite artist (OR:1.18, 95%CI: 1.04-1.33, p=0.009) who smoke, f) protective factors against smoking: participation in sports (OR:0.59, 95%CI: 0.53-0.67, p<0.001), watching television (OR:0.74, 95%CI 0.66-0.84, p<0.001) and influence by health warning messages on cigarette packets (OR:0.42, 95%CI: 0.37, 0.48, p<0.001). CONCLUSIONS: Even though prevalence of cigarette smoking is not too high among Greek adolescents, frequency of everyday cigarette use is alarming. We identified many social and lifestyle risk and preventive factors that should be incorporated in a national smoking prevention program among Greek adolescents.

Chest imaging and lung function impairment after long-term occupational exposure to low concentrations of chrysotile.

The aim of the present study was the investigation of radiographic findings in relation to lung function after occupational exposure to permissible levels of relatively pure chrysotile (0.5-3% amphiboles). We studied 266 out of the total 317 employees who have worked in an asbestos cement factory during the period 1968-2004 with chest x-ray, high-resolution computed tomography (HRCT) and lung function tests. Sensitivity of chest x-ray was 43% compared to HRCT. Abnormal HRCT findings were found in 75 subjects (67%) and were related to age, occupational exposure duration, and spirometric data. The presence of parenchymal or visceral pleural lesions (exclusively or as the predominant abnormality) was being accompanied by lower total lung capacity and diffusion capacity. HRCT was much more sensitive than chest x-ray for occupational chrysotile exposure. Lung function impairment was related with parenchymal but not with pleural HRCT abnormalities.

Pulmonary rehabilitation in non-small cell lung cancer patients after completion of treatment.

OBJECTIVES: The functional status of patients with non-small cell lung cancer (NSCLC) is often limited not only by cancer itself, but also by the different types of treatment and by comorbidities [eg, chronic obstructive pulmonary disease (COPD), congestive heart failure]. The aim of this study was to investigate the utility of an inpatient multidisciplinary pulmonary rehabilitation (PR) program on pulmonary function and exercise capacity of patients with NSCLC after completion of their treatment. METHODS: Forty-seven patients with NSCLC underwent a PR program after completing cancer treatment. Pulmonary function tests, arterial blood gases, 6-minute walk test, and dyspnea severity before and after PR were retrospectively analyzed. RESULTS: After undergoing PR, patients exhibited significantly higher forced expiratory volume in the first second (mean increase, 110 ± 240 mL; P=0.007), forced vital capacity (mean increase, 130 ± 290 mL; P=0.001), and 6-minute walk test distance (mean increase, 41 m; P<0.001). A statistically significant improvement in the severity of dyspnea (mean decrease in the Modified Medical Research Council dyspnea scale: 0.26 ± 0.61; P=0.007) was observed. We observed that improvement in pulmonary function and exercise capacity was similar among patients with and without COPD and among patients who underwent thoracic surgery or not. CONCLUSIONS: Patients with NSCLC who could accomplish PR program, after multidisciplinary treatment for the main disease, seem to benefit in terms of exercise capacity and pulmonary function. These benefits are independent of concurrent COPD and surgical treatment for lung cancer.

Prevalence and risk factors for initiation of smoking in Greek high-school students.

The smoking habits of 9,276 high-school students (15-18 years old) in six cities of Northern Greece were studied using a questionnaire in order to determine the prevalence and possible risk factors for initiation of smoking. We observed that 29.6% of high-school students (32.6% of boys and 26.7% of girls) were current smokers. A percentage of 43.3% had started smoking before the age of 14. Reactive behaviour towards parents' and teachers' advice (40.2%) and the existence of smoking friends (40.1%) were the main reasons of initiation. A well-planned integrated anti-smoking campaign is urgently required, especially among students and teachers.

Efficacy and safety of erythromycin as sclerosing agent in patients with recurrent malignant pleural effusion.

OBJECTIVES: The aim of pleurodesis in malignant pleural effusions is to prevent reaccumulation of the fluid, symptoms, and avoid the need for repeated hospitalization for thoracentesis. The purpose of this study was to evaluate the efficacy and safety of erythromycin as a pleural sclerosing agent. METHODS: Over a 2-year period, 34 patients with a symptomatic, recurrent, malignant pleural effusion who referred for chest tube drainage and pleurodesis were included. They had not received prior intrapleural therapy and had predicted survival of at least 1 month. All underwent pleural drainage and chemical pleurodesis with erythromycin. Complications and response to pleurodesis, according to clinical and radiographic criteria after 90 days, were recorded. RESULTS: The overall response was 88.2%. Complete response (no reaccumulation of pleural fluid after 90 days) was observed in 27 patients (79.4%). Partial response (reaccumulation of fluid but without symptoms, not requiring drainage) was observed in 3 (8.8%). No response (symptomatic reaccumulation of fluid that required drainage) was observed in 4 (11.8%). All patients experienced pleurodynia that was treated with administration of paracetamol and/or dextropropoxyphene. Sinus tachycardia and concurrent mild systemic hypertension were observed 2 and 4 hours after pleurodesis. Both of them were attributed to pleurodynia as there was remission with analgesics. CONCLUSIONS: This study suggests that erythromycin is effective and safe as a sclerosing agent for pleurodesis in patients with recurrent malignant pleural effusions.

The validity of the diagnosis of chronic obstructive pulmonary disease in general practice.

AIM: To determine the validity of the diagnosis of chronic obstructive pulmonary disease (COPD) in general practice in patients given a diagnosis of COPD and treated with bronchodilators. METHODS: From the medical records of eight Health Centres in Northern Greece, 319 subjects aged over 40 years and diagnosed as "COPD" were entered into the study. All filled in a special questionnaire and were subjected to spirometry, rhinomanometry and chest X-ray. RESULTS: One hundred and sixty patients (50.2%) met the GOLD criteria for COPD. Twenty-six of them were non-smokers and underwent further evaluation: blood eosinophil count, serum IgE assay, high resolution computed tomography (HRCT) scan of the chest, and echocardiography; 16 were given a different diagnosis. One hundred and fifty-nine subjects (49.8%) with an FEV1/ FVC ratio >0.7 did not meet the GOLD criteria for COPD; 71 suffered from nasal obstruction, 13 from asthma, six had restrictive pulmonary disease and 69 had no respiratory disease. CONCLUSION: Diagnostic errors in patients with respiratory symptoms in the primary healthcare setting are frequent. Patients suspected to have COPD should undergo spirometry testing after bronchodilation. An alternative diagnosis must be sought for non-smoking patients with irreversible airway obstruction.