The national alpha-1 antitrypsin deficiency registry in Poland.

The alpha-1 antitrypsin deficiency (AATD) targeted screening program, together with the National Registry, were established in Poland in 2010 soon after the AATD diagnostics became available. Between 2010 and 2014 a total of 2525 samples were collected from respiratory patients countrywide; 55 patients with severe AAT deficiency or rare mutations were identified and registered, including 36 PiZZ subjects (65%). The majority of AATD patients were diagnosed with COPD (40%) or emphysema (7%), but also with bronchial asthma (16%) and bronchiectasis (13%). Therefore, the registry has proved instrumental in setting-up the AATD-dedicated network of respiratory medical centres in Poland. Since augmentation therapy is not reimbursed in our country, the smoking cessation guidance, optimal pharmacotherapy of respiratory symptoms as well the early detection, and effective treatment of exacerbations is absolutely essential.

Application of impulse oscillometry in respiratory system evaluation in elderly patients.

INTRODUCTION: Spirometry, which is a basic diagnostic tool of the respiratory system, may cause problems to patients of advanced age because of required cooperation and specific respiratory manoeuvres. Impulse oscillometry (IOS) may be an interesting alternative for spirometry as the examination is made during quiet breathing and gives information about resistive properties of the respiratory system. MATERIAL AND METHODS: This work presents the results of oscillometric measurements made in 277 patients aged 65-96 years, in whom spirometry was also performed. RESULTS: Resistances measured with IOS (R5, R5-R20) and the resonant frequency Fn correlated significantly with FEV1 (r = -0.503; -0.570 and -0.673, respectively). A comparison of the results from patients with airway obstruction confirmed in spirometry with those of the non-obstructed group showed highly significant differences in mean values of oscillometric parameters (p < 0.001). CONCLUSIONS: As R5-R20 is regarded as a measure of peripheral airways resistance, IOS may serve as an interesting complementary or alternative method for spirometry in elderly subjects for evaluation of the state of respiratory system.

Quality of spirometry in the elderly.

INTRODUCTION: Spirometry is the basic method used to diagnose and monitor obstructive diseases. Spirometric tests are performed in more and more people of advanced age (more than 65 years old). The objective of the study was to assess the quality of spirometry (measurement of the flow-volume curve) in subjects of the aforementioned age group, with reference to applicable quality criteria specified in guidelines ERS/ATS 2005 and PTChP 2006. MATERIAL AND METHODS: The study was of a retrospective nature. The authors analysed the results of spirometry performed in 1271 subjects who were 65 to 94 years old and who underwent spirometric tests in the Respiratory Physiopathology Laboratory of Kujawy-Pomorze Regional Centre of Pulmonology in Bydgoszcz over a period of 6 months. This group included 759 males (average age 73.2 ± 5.9 years) and 512 females (average age 73.2 ± 5.7 years). The quality of the spirometry was assessed according to error codes assigned to individual spirometric sessions by the software JLab 5.31 installed in the measuring system MasterScreen (CareFusion). RESULTS: Twenty-nine (2.3%) of the 1271 subjects failed to perform spirometric measurements. For the remaining 1242 subjects the following spirometry quality was determined: correctly performed spirometric test in 415 (33.4%) subjects; one error in 673 (54.2%) subjects; 2 errors in 136 (11%) subjects; 3 errors in 15 (1.2%) subjects and 4 errors in 3 (0.2%) subjects. The analysis of individual errors revealed that the lack of a plateau at the end of exhalation was found in 747 (60.1%) subjects (including only 25 (2%) subjects with FET < 6 s); increased BEV value in 7 (0.6%) subjects; abruptly finished exhalation in 36 (2.9%) subjects; and no FVC and FEV1 repeatability in 43 (3.5%) and 169 (13.6%) subjects, respectively. CONCLUSIONS: The most common error was the lack of a plateau at the end of exhalation. Therefore, paying particular attention to the final phase of exhalation during spirometry should, as a result, increase the percentage of correctly performed spirometric tests in the elderly.

Efficacy of oral amantadine among patients hospitalised with COVID-19: A randomised, double-blind, placebo-controlled, multicentre study.

BACKGROUND: Amantadine has been proposed as a treatment for COVID-19 because it shows anti-SARS-CoV-2 activity in vitro. However, to date, no controlled study has assessed the safety and efficacy of amantadine in COVID-19. RESEARCH QUESTION: Whether amantadine is effective and safe among patients with different COVID-19 severity classifications. STUDY DESIGN: and Methods: This was multi-centre, randomised, placebo-controlled study.Patients with oxygen saturation ≤94% and no need for high-flow oxygen or ventilatory support were randomly allocated to receive oral amantadine or placebo (1:1) for 10 days in addition to standard care. The primary endpoint was time to recovery assessed over 28 days since randomisation, defined as discharge from hospital or no need for supplemental oxygen. RESULTS: The study was terminated early due to a lack of efficacy after an interim analysis. Final data from 95 patients who received amantadine (mean age, 60.2 years; 65% male; 66% with comorbidities) and 91 patients who received placebo (mean age, 55.8 years; 60% male; 68% with comorbidities) were obtained. The median (95% CI) time to recovery was 10 days both in the amantadine (9-11) and placebo arms (8-11; subhazard ratio = 0.94 [95%CI 0.7-1.3]). The percentage of deaths and percentage of patients who required intensive care at 14 and 28 days did not significantly differ between the amantadine and placebo groups. INTERPRETATION: Adding amantadine to standard care in patients hospitalised with COVID-19 did not increase the likelihood of recovery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04952519; www. CLINICALTRIALS: gov.

[Comparison of the results of long term oxygen therapy in patients treated sequentially using stationary or a portable source of oxygen]. / Porównanie wyników domowego leczenia tlenem u chorych leczonych sekwencyjnie za pomoca stacjonarnego i przenosnego zródla tlenu.

INTRODUCTION: In long term oxygen therapy (LTOT) two oxygen sources are used, i.e. the stationary oxygen concentrator (OC) and portable liquid oxygen (LO). Polish NHS reimburses stationary oxygen sources only. The aim of this study was to compare the effect of change from OC into LO in patients treated using LTOT. MATERIAL AND METHODS: The study involved 30 patients qualified to LTOT. The degree of dyspnoea intensity, (MRC, Borg scale), exercise tolerance (6MWT), fitness, daily use of oxygen therapy, red blood count, lung function, number of exacerbations as well as health related quality of life (SGRQ) were assessed before introduction of LTOT, after 6 months of oxygen therapy using OC and after 6 months from change into LO. RESULTS: During first 6 months RBC decreased from 5.4 to 5.1 (p < 0.0001), HTC from 50.1% to 47.8% (p < 0.0001), 6MWD increased from 337.7 to 378.7 m (p < 0.0001), SGRQ score improved from 72.1 points to 64.4 points (p < 0.0001). Treatment with LO resulted in further improvement in studied parameters: RBC decreased from 5.1 to 4.8 (p < 0.0001), HTC from 47.8% to 44.3% (p < 0.0001), 6MWD increased from 378.7 m to 413 m (p < 0.0001), SGRQ score improved from 64.4 points to 54.9 points (p < 0.0001). Significant increase in daily oxygen breathing hours from 13.7 to 18.9 (p < 0.0001) was also observed. CONCLUSIONS: Use of liquid oxygen enables oxygen therapy at home and during ambulation and increases oxygen breathing hours, thus improving red blood count, exercise capacity and health related quality of life.

Development of Home Mechanical Ventilation in Poland in 2009-2019 Based on the Data of the National Health Fund.

Home mechanical ventilation (HMV) is a dynamically developing field of medicine driven by the increasing number of patients and technological advancements. In Poland, HMV has been financed from public funds since 2004. However, the organization of HMV is still evolving in search of the optimal model of care. The aim of this study was to analyze 11 years of HMV in terms of the number of patients, modes of ventilation, diagnosis and regional prevalence. In retrospective analysis of data reported to the National Health Fund by all health entities providing HMV in Poland in the period from 2009 to 2019, the following variables were included: age, sex, date of commencement, ventilation mode, diagnosis, and place of treatment. The diseases were identified according to the ICD-10 codes. A total of 12,616 patients receiving HMV were reported, including 1221 children (9.7%). The HMV prevalence increased from 2.8 in 2009 to 20/100,000 in 2019. In adults, the highest increase was reported for patients with chronic obstructive pulmonary disease, who accounted for 39% of all HMV users in 2019. The proportion of noninvasive ventilation (NIV) increased from 56% in 2014 to 73% in 2019. We identified significant regional variations in the prevalence of HMV between provinces. The main drivers for HMV development include full reimbursement, the development of hospital NIV centers and the involvement of respiratory physicians in the referral process for HMV.

Validation of the Polish version of Severe Respiratory Insufficiency Questionnaire.

INTRODUCTION: Improvement in the quality of life (QoL) is an essential outcome in patients with chronic respiratory failure (CRF). However, its reliable and comparative assessment is difficult in this highly heterogeneous group of patients. Severe Respiratory Insufficiency Questionnaire (SRI) has shown to have high psychometric properties to measure specific health-related QoL in patients with CRF due to different pathologies. OBJECTIVES: The aim of this study was to validate the Polish version of the SRI. PATIENTS AND METHODS: The Polish version of the SRI was created according to the procedure of translation and back­ translation of the original version. Patients with CRF treated with long­term oxygen therapy (LTOT) or home mechanical ventilation (HMV) were invited to the study. Polish SRI and 36­ Item Short Form Health Survey (SF­36) questionnaires were completed during 2 consecutive visits scheduled at a 2-4 week interval. The results were statistically tested for validity, viability, and reliability. The time and ability of completing, sociodemographic and clinical data were recorded. RESULTS: A total of 113 patients were enrolled. Seventy­ five participants (66%) completed the questionnaires without any assistance. A significant concurrent validity was confirmed by a correlation analysis between the SRI and the SF­36 scales. An exploratory factor analysis explained 69% of the variance of the questionnaire. High internal consistency was proved by the Cronbach α coefficient 0.951 for the Summary Scale. Repeatability was very high for all subscales (intraclass correlation coefficient, 0.871-0.915) and for the summary score (0.923, P <0.001). CONCLUSIONS: Our study demonstrated that the Polish version of the SRI is valid, reliable, and reproducible and may be used in research involving CRF.

[Prevalence of home mechanical ventilation in Poland]. / Rozpowszechnienie wentylacji mechanicznej w warunkach domowych w Polsce.

INTRODUCTION: Home mechanical ventilation (HMV) is increasingly used in the treatment of chronic respiratory failure thanks to rapid technological development, increasing number of elderly people and extension of indications. The aim of the study was to assess: prevalence of HMV in Poland, the proportions of lung disease and neuromuscular patients using HMV and the type of interface (invasive v. non-invasive). MATERIAL AND METHODS: The questionnaire was send to all institutions providing HMV in Poland and to regional departments of National Health System (NHS). RESULTS: All NHS departments responded. They reported 846 HMV users, 31% of children. The prevalence of HMV in Poland was assessed as 2,2 patient per 100.000 population without striking differences between provinces. Among 39 HMV centers in Poland 12 (31%) answered. They reported 206 patients (24% of all HMV users). Proportion of ventilation mode consisted of 59% (122 pts) treated via a tracheostomy and 41% (84 pts) with non invasive ventilation (NIV). 168 patients (82%) had neuromuscular diseases (ND), majority of them muscular dystrophy - 57 patients ( 34% of ND) and amyotrophic lateral sclerosis - 39 patients (23% of ND). There were only 38 patients (18%) with lung and thoracic cage diseases: 17 with COPD and 10 with kyphoscoliosis. CONCLUSIONS: The prevalence of HMV treatment in Poland has developed dramatically in the last decade, but is still very low comparing to other European countries, especially due to very low number of patients with lung and chest wall diseases. The prevalence of invasive mode of ventilation is extremely high. The most important factors which inhibit development of HMV in Poland are: omission of respiratory physicians in the process of qualification, lack of national guidelines, sophisticated demands for HMV providers. The awareness of the need of HMV especially in patients with respiratory failure due to obesity hypoventilation syndrome and restrictive lung diseases should be increased among chest physicians.

Treatment of acute respiratory failure in the course of COVID-19. Practical hints from the expert panel of the Assembly of Intensive Care and Rehabilitation of the Polish Respiratory Society.

In 2019, a pandemic began due to infection with a novel coronavirus, SARS-CoV-2. In many cases, this coronavirus leads to the development of the COVID-19 disease. Lung damage in the course of this disease often leads to acute hypoxic respiratory failure and may eventually lead to acute respiratory distress syndrome (ARDS). Respiratory failure as a result of COVID-19 can develop very quickly and a small percent of those infected will die because of it. There is currently no treatment for COVID-19, therefore the key therapeutic intervention centers around the symptomatic treatment of respiratory failure. The main therapeutic goal is to main-tain gas exchange, mainly oxygenation, at an appropriate level and prevent the intensification of changes in the lung parenchyma. Depending on the severity of hypoxemia different techniques can be used to improve oxygenation. Medical staff dealing with COVID-19 patients should be familiar with both, methods used to treat respiratory failure and the epidemiological risks arising from their use. In some patients, conventional (passive) oxygen therapy alone is sufficient. In patients with worsening respiratory failure high flow nasal oxygen therapy (HFNOT) may be effective. The continuous positive airway pressure (CPAP) and non-invasive ventilation (NIV) methods can be used to a limited extent. With further disease progression, invasive ventilation must be used and in special situations, extracorporeal membrane oxygenation (ECMO) can also be administered. The authors of this article set themselves the goal of presenting the most current knowledge about the epidemiology and patho-physiology of respiratory failure in COVID-19, as well as the methods of its treatment. Given the dynamics of the developing pandemic, this is not an easy task as new scientific data is presented almost every day. However, we believe the knowledge contained in this study will help doctors care for patients with COVID-19. The main target audience of this study is not so much pneumonologists or intensivists who have extensive experience in the application of the techniques discussed here, but rather doctors of other specializations who must master new skills in order to help patients during the time of a pandemic.

Spirometry during the SARS-CoV-2 pandemic. Guidelines and practical advice from the expert panel of Respiratory Physiopathology Assembly of Polish Respiratory Society.

At the end of 2019, in Wuhan, the Hubei Province's capital city in China, the first cases of COVID-19 disease caused by the novel coronavirus, SARS-CoV-2, were described. The rapid spread of the infection through the world resulted in the World Health Organization announcing the COVID-19 a global pandemic in March 2020. The main routes of transmission of the novel coronavirus SARS-CoV-2, according to current evidence, are via droplets inhalation, direct contact with contaminated surfaces, and transmission via the mucous membranes of the mouth, nose, and eyes, and probably through airborne particles from the respiratory tract, generated during coughing and sneezing of infected individuals. During the pulmonary function testing (PFTs), which require strenuous breathing maneuvers and generate high-intensity airflow, aerosols, and micro-aerosols are formed from respiratory secretions and may contain viral and bacterial particles. Therefore, such forced respiratory maneuvers pose a significant risk of spreading the infection to patients and laboratory staff. According to current knowledge, the source of infection may also be an asymptomatic and a pre-symptomatic individual. Coronavirus SARS-CoV-2 has been increasingly prevalent in the community, and this increases a potential risk to all patients tested lung function and staff working there. As the patients' and staff's safety is of unprecedented importance, the additional precautions when performing pulmonary function tests are necessary and unquestionable. In consequence, the greater availability of consumables and personal protective equipment is indispensable. The reorganization of daily practice will prolong test time, reduce the number of tests performed, and slow down patients' flow. The guidance provides practical advice to health care professionals on performing pulmonary function tests during the COVID-19 pandemic. It has been developed basing on currently available information and recommendations from relevant health care institutions. As the COVID-19 pandemic is a rapidly evolving situation and the new scientific data has been becoming are available, the guidance will be updated over time.

Analysis of hospital management of chronic respiratory diseases in light of the "Maps of Health Needs" project in Poland.

INTRODUCTION: The "Maps of Health Needs" project has been carried out in Poland since 2016 and its purpose is to implement quality-promoting and organisational solutions in the Polish healthcare system. This paper is the analysis of hospitalisations for chronic respiratory diseases recorded in Polish National Health Fund databases in 2014. MATERIAL AND METHODS: The study included 122,000 hospitalisations of adults and 22,000 hospitalisations of children. Epidemio-logical parameters (incidence and prevalence) and major hospitalisation parameters were determined through statistical analysis. RESULTS: The highest registered incidence was observed in asthma patients (548 per 100,000 inhabitants) followed by COPD patients (233 per 100,000 inhabitants). Asthma patients were also characterised by the highest prevalence, with lower values being observed in COPD patients. In the group of adults, patients aged 65 years or older and 80 years or older accounted for 44% and 14% of hospitalised adults respectively. The analysis also revealed that 66% of hospitalisations of adults included patients with asthma, COPD and respiratory failure. The development of respiratory failure prolongs hospitalisation and increases both in-hospital and post-discharge mortality. In children, 90% of the identified hospitalisations were for asthma, chronic inflammatory lung diseases and cystic fibrosis. CONCLUSIONS: The results of the study demonstrate that pulmonary obstructive diseases are associated with a considerable burden. Therefore, corrective actions within the Polish healthcare system are required to decrease the number of hospitalisations for these diseases.

[The management of obstructive sleep apnea syndrome in drivers - recommendations of the Polish Society Of Occupational Medicine, The Polish Respiratory Society, The Nofer Institute of Occupational Medicine in Lodz and The Polish Sleep Research Society]. / Postepowanie lekarskie w obturacyjnym bezdechu sennym u osób kierujacych pojazdami − zalecenia Polskiego Towarzystwa Medycyny Pracy, Polskiego Towarzystwa Chorób Pluc, Instytutu Medycyny Pracy w Lodzi i Polskiego Towarzystwa Badan nad Snem.

The findings of numerous studies and analyzes conducted in many countries have proven that obstructive sleep apnea (OSA) negatively affects the psychophysical abilities drivers. Therefore, in Commission Directive 2014/85/EU of July, 1 2014, OSA was recognized as one of the most important risk factors for car accidents. The implementation of said Directive by Member States is to contribute to reducing the risk of such accidents. The implementation of the Directive in Poland has resulted in enacting the Ordinance of the Minister of Health of December 23, 2015 amending the ordinance on medical examinations of applicants for a driving license and drivers. Although Annex 2 to that regulation sets out the detailed conditions for a medical examination for OSA, it does not regulate or clarify the issue of tools and methods for suspecting OSA in a moderate or hard form. Therefore, it was necessary to develop standards of management for doctors authorized to perform medical examinations of drivers and applicants for a driving license in the case of suspected OSA. The paper presents an algorithm of proceedings that streamlines the case-law process in the above-mentioned cases, which was developed by the Polish Society of Occupational Medicine in cooperation with the Polish Respiratory Society, the Nofer Institute of Occupational Medicine in Lódz and the Polish Sleep Research Society. Med Pr. 2020;71(2):233-43.

Validation of the Polish-language version of the COPD Assessment Test.

INTRODUCTION: The COPD Assessment Test (CAT) is a standardized patient-completed tool dedicated to assessment of symptom severity. While the Polish CAT version has been used for a few years, it has not been validated so far. OBJECTIVES: The aim of the study was to validate the Polish­language version of the CAT questionnaire by assessing its reproducibility and reliability. PATIENTS AND METHODS: Validation of the Polish­language version of the CAT questionnaire was a substudy of the international multicenter observational cross­sectional POPE survey of patients with chronic obstructive pulmonary disease (COPD) in Central and Eastern European countries. The study was completed in 395 outpatients with stable disease at least 4 weeks before the survey. Validation was performed with the use of the Spearman correlation and Cronbach α coefficients, Cohen κ test, and the Bland-Altman procedure. RESULTS: The internal consistency assessed by the Cronbach α coefficient was 0.87 for the questionnaire and 0.84 to 0.86 for its separate items. The repeatability of the questionnaire was good to very good (Cohen κ, 0.76-0.85; P <0.01). The Spearman coefficient for the sum of scores of test-retest responses was 0.95 (P <0.01). The Bland-Altman analysis revealed very good test-retest and interrater reliability, with the mean difference between test I and test II results of -0.556 (95% CI, -0.345 to 0.767). CONCLUSIONS: The Polish version of the CAT questionnaire is a reproducible and reliable instrument for evaluation of patients with COPD and should be recommended for use in clinical practice.

The prevalence of tobacco smoking and attitudes of Polish pulmonologists towards smoking.

INTRODUCTION: Pulmonologists can play an important role in smoking prevention and control. The aim of this study was to assess smoking prevalence among Polish pulmonologists and physicians' behaviour towards smoking patients. MATERIAL AND METHODS: The study was performed in 2006 during national congress of Polish Respiratory Society. The survey was performed using a questionnaire including questions regarding age, sex, professional activities, specialty, academic degree and respondents' nicotine status, attitude and activity towards smoking patients. RESULTS: Questionnaires were filled in by 498 physicians: 160 (32.1%) men and 338 (67.9%) women, out of 852 participating physicians (58.5%) who received the questionnaire. There were 11.3% smokers (13.8% men and 10% women), 25.1% of surveyed physicians were ex-smokers, and 63.6% never smokers. 91.4% of respondents always ask patients if they smoke. 87.4% physicians always advise smoking cessation to their patients, but smoking cessation support is offered only by 48% of respondents. Almost half respondents use drugs in nicotine dependence treatment. Majority of respondents (81.1%) think that physician's attitude influences patient's behaviour. More than a half (55.7%) think that smoking by physicians is not in accordance with physician's ethics. 91.4% support smoking ban in public places. CONCLUSIONS: This study found a lower prevalence of smoking among Polish pulmonologists compared with the general population, and with the previous surveys and demonstrated the impact of personal smoking on physicians' attitudes towards smoking.

Distribution and characteristics of COPD phenotypes - results from the Polish sub-cohort of the POPE study.

Background: This study aimed to examine the distribution of predefined phenotypes, demographic data, clinical outcomes, and treatment of patients who were included in the Polish cohort of the Phenotypes of COPD in Central and Eastern Europe (POPE) study. Patients and methods: This was a sub-analysis of the data from the Polish cohort of the POPE study, an international, multicenter, observational cross-sectional survey of COPD patients in Central and Eastern European countries. The study included patients aged >40 years, with a confirmed diagnosis of COPD, and absence of exacerbation for at least 4 weeks before study inclusion. A total of seven Polish centers participated in the study. Results: Among the 430 Polish COPD patients enrolled in the study, 61.6% were non-exacerbators (NON-AE), 25.3% were frequent exacerbators with chronic bronchitis (AE CB), 7.9% were frequent exacerbators without chronic bronchitis (AE NON-CB), and 5.1% met the definition of asthma-COPD overlap syndrome (ACOS). There were statistically significant differences among these phenotypes in terms of symptom load, lung function, comorbidities, and treatment. Patients with the AE CB phenotype were most symptomatic with worse lung function, and more frequently reported anxiety and depression. Patients with the ACOS phenotype were significantly younger and were diagnosed with COPD earlier than those with other COPD phenotypes; those with the ACOS phenotype were also more often atopic and obese. Conclusion: There is significant heterogeneity among COPD patients in the Polish population in terms of phenotype and clinical outcome. The non-exacerbator phenotype is observed most frequently in Poland, while the frequent exacerbator with chronic bronchitis phenotype is the most symptomatic.

Does urinary peptide content differ between COPD patients with and without inherited alpha-1 antitrypsin deficiency?

Differentiating between chronic obstructive pulmonary disease (COPD) patients with normal (PiMM) or deficient (PiZZ) genetic variants of alpha-1 antitrypsin (A1AT) is important not only for understanding the pathobiology of disease progression but also for improving personalized therapies. This pilot study aimed to investigate whether urinary peptides reflect the A1AT-related phenotypes of COPD. Urine samples from 19 clinically stable COPD cases (7 PiMM and 12 PiZZ A1AT) were analyzed by capillary electrophoresis coupled to mass spectrometry. We identified 66 peptides (corresponding to 36 unique proteins) that differed between PiZZ and PiMM COPD. Among these, peptides from the collagen family were the most abundant and divergent. A logistic regression model based on COL1A1 or COL5A3 peptides enabled differentiation between PiMM and PiZZ groups, with a sensitivity of 100% and specificity of 85.71% for COL1A1 and a sensitivity of 91.67% and specificity of 85.71% for COL5A3. Furthermore, patients with PiZZ presented low levels of urinary peptides involved in lipoproteins/lipids and retinoic acid metabolism, such as apolipoprotein A-I and C4, retinol-binding protein 4 and prostaglandin-H2 D-isomerase. However, peptides of MDS1 and EVII complex locus, gelsolin and hemoglobin alpha were found in the urine of COPD cases with PiZZ, but not with PiMM. These capillary electrophoresis coupled to mass spectrometry-based results provide the first evidence that urinary peptide content differs between PiMM and PiZZ patients with COPD.