A Real-World Multicenter Retrospective Observational Study on Polish Experience with Nintedanib Therapy in Patients with Idiopathic Pulmonary Fibrosis: The PolExNIB Study.

Nintedanib is a disease-modifying agent licensed for the treatment of IPF. Data on Polish experience with nintedanib in IPF are lacking. The present study aimed to describe the safety and efficacy profiles of nintedanib in a large real-world cohort of Polish patients with IPF. This was a multicenter, retrospective, observational study of IPF patients treated with nintedanib between March 2018 and October 2021. Data collection included baseline clinical characteristics, results of pulmonary function tests (PFTs), and a six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), and treatment persistence were also retrieved. A total of 501 patients (70% male) with a median age of 70.9 years (IQR 65-75.7) were included in this study. Patients were followed on treatment for a median of 15 months (7-25.5). The majority of patients (66.7%) were treated with the full recommended dose of nintedanib and 33.3% of patients were treated with a reduced dose of a drug. Intermittent dose reductions or drug interruptions were needed in 20% of patients. Over up to 3 years of follow-up, pulmonary function remained largely stable with the minority experiencing disease progression. The most frequent ADRs included diarrhea (45.3%), decreased appetite (29.9%), abdominal discomfort (29.5%), weight loss (32.1%), nausea (20.8%), fatigue (19.2%), increased liver aminotransferases (15.4%), and vomiting (8.2%). A total of 203 patients (40.5%) discontinued nintedanib treatment due to diverse reasons including ADRs (10.2%), death (11.6%), disease progression (4.6%), patient's request (6.6%), and neoplastic disease (2.2%). This real-world study of a large cohort of Polish patients with IPF demonstrates that nintedanib therapy is safe, and is associated with acceptable tolerance and disease stabilization. These data support the findings of previously conducted clinical trials and observational studies on the safety and efficacy profiles of nintedanib in IPF.

Guidelines of the Polish Respiratory Society on the Diagnosis and Treatment of Progressive Fibrosing Interstitial Lung Diseases Other than Idiopathic Pulmonary Fibrosis.

The recommendations were developed as answers to previously formulated questions concerning everyday diagnostic and therapeutic challenges. They were developed based on a review of the current literature using the GRADE methodology. The experts suggest that PF-ILD be diagnosed based on a combination of different criteria, such as the aggravation of symptoms, progression of radiological lesions, and worsening of lung function test parameters. The experts recommend a precise diagnosis of an underlying disease, with serological testing for an autoimmune disease always being included. The final diagnosis should be worked out by a multidisciplinary team (MDT). Patients with an interstitial lung disease other than IPF who do not meet the criteria for the progressive fibrosis phenotype should be monitored for progression, and those with systemic autoimmune diseases should be regularly monitored for signs of interstitial lung disease. In managing patients with interstitial lung disease associated with autoimmune diseases, an opinion of an MDT should be considered. Nintedanib rather than pirfenidon should be introduced in the event of the ineffectiveness of the therapy recommended for the treatment of the underlying disease, but in some instances, it is possible to start antifibrotic treatment without earlier immunomodulatory therapy. It is also admissible to use immunomodulatory and antifibrotic drugs simultaneously. No recommendations were made for or against termination of anti-fibrotic therapy in the case of noted progression during treatment of a PF-ILD other than IPF. The experts recommend that the same principles of non-pharmacological and palliative treatment and eligibility for lung transplantation should be applied to patients with an interstitial lung disease other than IPF with progressive fibrosis as in patients with IPF.

Guidelines of the Polish Respiratory Society on the Diagnosis and Treatment of Progressive Fibrosing Interstitial Lung Diseases Other than Idiopathic Pulmonary Fibrosis

The recommendations were developed as answers to previously formulated questions concerning everyday diagnostic and therapeutic challenges. They were developed based on a review of the current literature using the GRADE methodology. The experts suggest that PF-ILD be diagnosed based on a combination of different criteria, such as the aggravation of symptoms, progression of radiological lesions, and worsening of lung function test parameters. The experts recommend a precise diagnosis of an underlying disease, with serological testing for an autoimmune disease always being included. The final diagnosis should be worked out by a multidisciplinary team (MDT). Patients with an interstitial lung disease other than IPF who do not meet the criteria for the progressive fibrosis phenotype should be monitored for progression, and those with systemic autoimmune diseases should be regularly monitored for signs of interstitial lung disease. In managing patients with interstitial lung disease associated with autoimmune diseases, an opinion of an MDT should be considered. Nintedanib rather than pirfenidon should be introduced in the event of the ineffectiveness of the therapy recommended for the treatment of the underlying disease, but in some instances, it is possible to start antifibrotic treatment without earlier immunomodulatory therapy. It is also admissible to use immunomodulatory and antifibrotic drugs simultaneously. No recommendations were made for or against termination of anti-fibrotic therapy in the case of noted progression during treatment of a PF-ILD other than IPF. The experts recommend that the same principles of non-pharmacological and palliative treatment and eligibility for lung transplantation should be applied to patients with an interstitial lung disease other than IPF with progressive fibrosis as in patients with IPF.

Therapeutic decisions in a cohort of patients with idiopathic pulmonary fibrosis: a multicenter, prospective survey from Poland.

Background: Pirfenidone and nintedanib are considered as the standard of care in idiopathic pulmonary fibrosis (IPF), but there is no consensus as to which of these two agents should be regarded as first-line treatment. Objective: To provide real-world data on therapeutic decisions of pulmonary specialists, particularly the choice of the antifibrotic drug in patients with IPF. Methods: This was a multicenter, prospective survey collecting clinical data of patients with IPF considered as candidates for antifibrotic treatment between September 2019 and December 2020. Clinical characteristics and information on the therapeutic approach were retrieved. Statistical evaluation included multiple logistic regression analysis with stepwise model selection. Results: Data on 188 patients [74.5% male, median age 73 (interquartile range, 68-78) years] considered for antifibrotic therapy were collected. Treatment was initiated in 138 patients, while 50 patients did not receive an antifibrotic, mainly due to the lack of consent for treatment and IPF severity. Seventy-two patients received pirfenidone and 66 received nintedanib. Dosing protocol (p < 0.01) and patient preference (p = 0.049) were more frequently associated with the choice of nintedanib, while comorbidity profile (p = 0.0003) and concomitant medication use (p = 0.03) were more frequently associated with the choice of pirfenidone. Age (p = 0.002), lung transfer factor for carbon monoxide (TLCO) (p = 0.001), and gastrointestinal bleeding (p = 0.03) were significantly associated with the qualification for the antifibrotic treatment. Conclusion: This real-world prospective study showed that dose protocol and patient preference were more frequently associated with the choice of nintedanib, while the comorbidity profile and concomitant medication use were more frequently associated with the choice of pirfenidone. Age, TLCO, and history of gastrointestinal bleeding were significant factors influencing the decision to initiate antifibrotic therapy.

IPF Respiratory Symptoms Management - Current Evidence.

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic disease of the lungs which is characterized by heavy symptom burden, especially in the last year of life. Despite recently established anti-fibrotic treatment IPF prognosis is one of the worst among interstitial lung diseases. In this review available evidence regarding pharmacological and non-pharmacological management of the main IPF symptoms, dyspnea and cough, is presented.

Expiratory central airway collapse - an overlooked entity?: Two case reports.

INTRODUCTION: Expiratory central airway collapse is defined by excessive inward bulging of either tracheobronchial posterior membrane or cartilage. The former is called excessive dynamic airway collapse (EDAC), and the latter, depending on the site of collapse, tracheomalacia, bronchomalacia or tracheobronchomalacia. Due to their non-specific symptoms and lack of awareness amongst clinicians they tend to be mislabeled as common obstructive lung disorders, or complicate their course undetected. Particular controversies refer to EDAC sometimes considered just as a symptom of obstructive lung disease and not a separate entity. Nonetheless, a growing body of evidence indicates that EDAC might be present in patients without apparent obstructive lung disease or it might be an independent risk factor in chronic obstructive pulmonary disease or asthma patients. PATIENT CONCERNS: Patient #1 was admitted because of idiopathic chronic cough whereas patient #2 was admitted for differential diagnosis of dyspnea of uncertain etiology. In both patients symptoms were unresponsive to bronchodilators and inhaled corticosteroids. FINDINGS AND DIAGNOSIS: In both patients an excess collapse of tracheobronchial posterior membrane was detected during bronchoscopy; in patient #1, of right main bronchus and right upper lobe bronchus and in patient #2 of right upper lobe bronchus and both main bronchi. Excess central airway collapse in patient #2 was also visualized on expiratory chest CT. In patient #1 spirometry did not reveal obturation, whereas in patient #2 only mild, irreversible, obstruction was revealed, disproportionate to patients significant breathlessness. INTERVENTIONS: Both patients were treated with N-acetylcysteine and adjustable positive expiratory pressure valves. OUTCOMES: Due to aforementioned treatment chronic cough in patient #1 subsided almost completely whereas patient's #2 dyspnea improved significantly. CONCLUSIONS: In presented cases EDAC was an unexpected finding, even though, it firmly corresponded with reported symptoms. Treatment modification led to improvement of patients quality of life.

A multicentre retrospective observational study on Polish experience of pirfenidone therapy in patients with idiopathic pulmonary fibrosis: the PolExPIR study.

BACKGROUND: Pirfenidone is an antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis (IPF). The drug is available for Polish patients with IPF since 2017. The PolExPIR study aimed to describe the real-world data (RWD) on the Polish experience of pirfenidone therapy in IPF with respect to safety and efficacy profiles. METHODS: This was a multicentre, retrospective, observational study collecting clinical data of patients with IPF receiving pirfenidone from January 2017 to September 2019 across 10 specialized pulmonary centres in Poland. Data collection included baseline characteristics, pulmonary function tests (PFTs) results and six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), treatment persistence, and survival were also collected up to 24 months post-inclusion. RESULTS: A total of 307 patients receiving pirfenidone were identified for analysis. The mean age was 68.83 (8.13) years and 77% were males. The median time from the first symptoms to IPF diagnosis was 15.5 (9.75-30) months and from diagnosis to start of pirfenidone treatment was 6 (2-23) months. Patients were followed on treatment for a median of 17 (12-22.75) months. Seventy-four patients (24.1%) required dose adjustments and 35 (11.4%) were chronically treated with different than the full recommended dose. A total of 141 patients (45.92%) discontinued therapy due to different reasons including ADRs (16.61%), death (8.79%), disease progression (6.51%), patient's own request (5.54%), neoplastic disease (3.91%) and lung transplantation (0.33%). Over up to 24 months of follow-up, the pulmonary function remained largely stable. The median annual decline in forced vital capacity (FVC) during the first year of pirfenidone therapy was -20 ml (-200-100) and during the second year was -120 ml (-340-30). Over a study period, 33 patients (10.75%) died. CONCLUSIONS: The PolExPIR study is a source of longitudinal RWD on pirfenidone therapy in the Polish cohort of patients with IPF supporting its long-term acceptable safety and efficacy profiles and reinforce findings from the previous randomised clinical trials and observational studies.

Guidelines of the Polish Respiratory Society for diagnosis and treatment of idiopathic pulmonary fibrosis.

INTRODUCTION: This document presents the guidelines of the Polish Respiratory Society (PTChP, Polskie Towarzystwo Chorób Pluc) for diagnosis and treatment of idiopathic pulmonary fibrosis (IPF), developed by agroup of Polish experts. MATERIAL AND METHODS: The recommendations were developed in the form of answers to previously formulated questions concer-ning everyday diagnostic and therapeutic challenges. They were developed based on acurrent literature review using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: We formulated 28 recommendations for diagnosis (8), pharmacological treatment (12) as well as non-pharma-cological and palliative therapy (8). The experts suggest that surgical lung biopsy (SLB) not be performed in patients with the probable usual interstitial pneumonia (UIP) pattern, with an appropriate clinical context and unanimous opinion of a multidisciplinary team. The experts recommend using antifibrotic agents in IPF patients and suggest their use irrespective of the degree of functional impairment. As regards non-pharmacological and palliative treatment, strong re-commendations were formulated regarding pulmonary rehabilitation, oxygen therapy (in patients with chronic respiratory failure), preventive vaccinations as well as referring IPF patients to transplant centres. Table 1 presents an aggregate list of recommendations. CONCLUSIONS: The Polish Respiratory Society Working Group developed guidelines for IPF diagnosis and treatment.

Histoplasmosis in an elderly polish tourist - a case report.

BACKGROUND: Histoplasmosis is a mycosis caused by soil-based fungus Histoplasma capsulatum endemic in the USA, Latin America, Africa and South-East Asia. The disease is usually self-resolving, but exposure to a large inoculum or accompanying immune deficiencies may result in severe illness. Symptoms are unspecific with fever, cough and malaise as the most common. Thus, this is a case of disease which is difficult to diagnose and very rare in Europe. As a result, it is usually not suspected in elderly patients with cough and dyspnea. CASE PRESENTATION: This is a case of a 78-year-old patient, admitted to our department due to respiratory failure, cough, shortness of breath, fever and weight loss with no response to antibiotics administered before the admission. Chest CT revealed numerous reticular and nodular infiltrations with distribution in all lobes. The cytopathology of BAL showed small parts of mycelium and numerous oval spores. Considering clinical presentation and history of travel to Mexico before onset of disease, pulmonary histoplasmosis was diagnosed. After introduction of antifungal treatment rapid improvement was achieved in terms of both clinical picture and respiratory function. CONCLUSIONS: Since the risk of Histoplasma exposure in Europe is minimal, patients, who present with dyspnea, fever and malaise are not primarily considered for diagnosis of histoplasmosis. However, taking into account increasing popularity of travelling, also by elderly or patients with impaired immunity, histoplasmosis should be included into differential diagnosis.

Atypical manifestations of granulomatosis with polyangiitis: the diagnostic challenge for pulmonologists.

This is a review considering atypical manifestations of granulomatosis with polyangiitis (GPA). Virtually any organ can be affected, and in some patients, GPA can manifest unusually. Since thoracic involvement of GPA often predominates, the first who might be expected to establish a diagnosis are pulmonary specialists. We would like to familiarize pulmonary specialists with several extra-ELK (E: ear-nose-throat; L: lung; K: kidney) involvements of the disease. We describe sites rarely affected by GPA like the breast, skeletal system, orbit and eye, heart and vessels, central nervous system, urogenital system as well as endocrine and gastrointestinal tract involvement.

Difficulties in the treatment of recurring diffuse alveolar hemorrhage accompanying primary antiphospholipid syndrome: a case report and literature review.

Pulmonary embolism is the most common pulmonary manifestation of primary antiphospholipid syndrome (PAPS). However, PAPS may manifest in the respiratory system also due to non-thrombotic processes. In the following paper we present a case of PAPS-related diffuse alveolar hemorrhage (DAH). Because of sparse literature and a lack of randomized controlled trials, there are currently no recommendations regarding the optimal choice of steroid-sparing agent in treating PAPS-related DAH. In our patient, treatment with cyclophosphamide or mycophenolate mofetil along with low dose prednisone was ineffective, partially because of infectious complications, whereas addition of monthly intravenous immunoglobulin to mycophenolate mofetil and prednisone, appears to control the disease.

High prevalence of carriers of variant c.1528G>C of HADHA gene causing long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) in the population of adult Kashubians from North Poland.

BACKGROUND/OBJECTIVES: The mitochondrial ß-oxidation of fatty acids is a complex catabolic pathway. One of the enzymes of this pathway is the heterooctameric mitochondrial trifunctional protein (MTP), composed of four α- and ß-subunits. Mutations in MTP genes (HADHA and HADHB), both located on chromosome 2p23, cause MTP deficiency, a rare autosomal recessive metabolic disorder characterized by decreased activity of MTP. The most common MTP mutation is long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency caused by the c.1528G>C (rs137852769, p.Glu510Gln) substitution in exon 15 of the HADHA gene. SUBJECTS/METHODS: We analyzed the frequency of genetic variants in the HADHA gene in the adults of Kashubian origin from North Poland and compared this data in other Polish provinces. RESULTS: We found a significantly higher frequency of HDHA c.1528G>C (rs137852769, p.Glu510Gln) carriers among Kashubians (1/57) compared to subjects from other regions of Poland (1/187). We found higher frequency of c.652G>C (rs71441018, pVal218Leu) polymorphism in the HADHA gene within population of Silesia, southern Poland (1/107) compared to other regions. CONCLUSION: Our study indicate described high frequency of c.1528G>C variant of HADHA gene in Kashubian population, suggesting the founder effect. For the first time we have found high frequency of rs71441018 in the South Poland Silesian population.

Recurrent haemoptysis as a symptom of severe pulmonary vein stenosis-a rare complication of catheter ablation in atrial fibrillation.

A pulmonary vein stenosis is a known adverse event of catheter ablation in atrial fibrillation. However, it should be considered due to high frequency of such procedures. Haemoptysis, a symptom of severe stenosis, is often misdiagnosed as other different diseases. We present a case report of a 52-year-old patient with recurrent haemoptysis, dyspnoea, and fatigue, which turned out to be complication after catheter ablation. Successful treatment with drug-eluting stent (DES) was implemented with vast clinical improvement and follow-up.

Smoking Status and the Five-Factor Model of Personality: Results of a Cross-Sectional Study Conducted in Poland.

Tobacco smoking is the single most important modifiable factor in increased morbidity and premature mortality. Numerous factors-including genetics, personality, and environment-affect the development and persistence of tobacco addiction, and knowledge regarding these factors could improve smoking cessation rates. This study compared personality traits between never, former, and current smokers, using the Five-Factor Model of Personality in a country with a turbulent smoking reduction process.: In this cross-sectional study, 909 Polish adults completed the Revised Neuroticism-Extraversion-Openness Personality Inventory. Our results showed that current smokers' scores for extraversion, one of the five global dimensions of personality, were higher relative to never smokers. Neuroticism, openness to experience, agreeableness, and conscientiousness did not differ significantly according to smoking status. Facet analysis, which described each dimension in detail, showed that current smokers' activity and excitement seeking (facets of extraversion) scores were higher relative to those of never and former smokers. In turn, current smokers' dutifulness and deliberation (facets of conscientiousness) scores were lower than those found in former and never smokers. Never smokers scored the highest in self-consciousness (a facet of neuroticism) and compliance (a component of agreeableness). The study conducted among Polish individuals showed variation in personality traits according to their smoking status; however, this variation differed from that reported in countries in which efforts to reduce smoking had begun earlier relative to Poland. Knowledge regarding personality traits could be useful in designing smoking prevention and cessation programs tailored to individuals' needs.

The usefulness of histopathological examinations of non-renal biopsies in the diagnosis of granulomatosis with polyangiitis.

INTRODUCTION: Granulomatosis with polyangiitis (GPA) is a rare, ANCA-associated, systemic disease characterized by necrotizing small and medium vessel vasculitis of unknown etiology associated with granulomatous inflammation affecting the renal, pulmonary, upper airways, ocular systems and other tissues. Histological proof of the granulomatosis with polyangiitis (GPA) can be obtained by biopsy of clinically involved sites. The main purpose of this study was to examine histopathological changes in non-renal biopsies from patients with established diagnosis of GPA and evaluated the histological confirmation at diagnosis of this disease. MATERIAL AND METHODS: A retrospective analysis was performed in patients with GPA diagnosed and treated in clinics of the University Clinical Center (UCK) in Gdansk in 1988-2009. RESULTS: In the analyzed group of GPA patients the histopathological examination of biopsies taken from involved tissues (except kidney) was performed in 60% of patients. Thirty-six out of 93 biopsies (39%) were diagnosed as typical of GPA, 10 (10.7%) were suggestive and 51 (54.8%) were non-specific. Considering all biopsies, the diagnosis was confirmed in 24 patients (57% of patients in whom biopsies were taken). Epitheloid cell granulomas were present in 33 biopsies (43%), characteristic necrosis in 27 biopsies (35%), small vessel vasculitis in 18 biopsies (23%), while multinucleated giant cells were identified only in 9 biopsies (12%). CONCLUSIONS: Histopathological examination of the affected tissues remains the gold standard of the diagnosis of GPA. Its usefulness increases, particularly in ANCA-negative patients, in the initial phase of the disease, or in patients with atypical clinical presentation. In many cases, it is necessary to repeat biopsy to establish the diagnosis. The role of the histopathological examination seems to be particularly important when ANCA is negative or clinical symptoms are atypical of GPA.

Association Between CHRNA3 and CHRNA5 Nicotine Receptor Subunit Gene Variants and Nicotine Dependence in an Isolated Populationof Kashubians in Poland.

BACKGROUND Genome-wide and allelic association studies have shown the contribution of CHRNA5-A3-B4 nicotinic receptor subunit gene cluster within chromosome 15 to nicotine dependence (ND). While an association between several single-nucleotide polymorphisms (SNPs) at that locus and smoking quantity (cigarettes per day; CPD) has been well recognized, there are some inconsistencies in demonstrating the influence of these SNPs on other ND phenotypes. This uncertainty motivated us to examine the association of 3 selected SNPs (CHRNA3 rs1051730, rs6495308, and CHRNA5 rs55853898) with ND in an isolated population of Kashubians from Poland. MATERIAL AND METHODS The study sample consisted of 788 current daily smokers. ND was assessed by CPD, the Fagerstrom Test for Nicotine Dependence (FTND), its brief version - Heavy Smoking Index (HSI), and time to first cigarette after waking (TTF). The correlation between studied SNPs and dichotomized values of ND measures was assessed in the regression analysis. Bonferroni corrected p-value of 0.017 was set for a type 1 error. RESULTS We found a robust association between risk allele A of rs1051730 and CPD >10 (odds ratio (OR)=1.77, 95% confidence interval (CI): 1.20-2.59, p=0.004), and a weak association, which did not survive correction for multiple testing, with FTND ³4. No associations between studied SNPs and HSI or TTF were demonstrated. CONCLUSIONS Our findings confirm that rs1051730 influences ND phenotype, as defined by CPD.

Nicotine dependence in an isolated population of Kashubians from North Poland: a population survey.

BACKGROUND: Tobacco use is a complex, multistage behaviour. The particular stages of this behaviour, including nicotine dependence (ND), are influenced by both genetics and the environment. Surveys on factors influencing tobacco use and ND, conducted in ethnically homogenous populations, can provide results less influenced by genetic and cultural heterogeneity. We aimed to assess ND in a sample of current smokers, derived from the geographically and culturally isolated population of Kashubians from North Poland, and evaluate its potential association with age, sex, and self-reported comorbidities. In addition, we attempted to replicate - for the first time in this population - previous findings on the association between ND and several variants within the CHRNA5A3-A5-B4 nicotine receptor subunit gene cluster. METHODS: The study sample consisted of 969 unrelated subjects who were all current smokers. ND was evaluated using four measures: the Fagerstrom Test for Nicotine Dependence (FTND), the Heavy Smoking Index (HSI), the number of cigarettes per day (CPD) and the time to first cigarette after waking (TTF). All subjects underwent genotyping for CHRNA5 rs16969968, CHRNA3 rs578776, and CHRNB4 rs12914008 variants. Multivariate regression analysis was used for the assessment of the studied correlations. A significance level of 0.05 with the Bonferroni correction for multiple testing was set for a type 1 error in the analyses. RESULTS: The mean CPD, FTND and HSI scores in the study sample were 17.3 ± 7.7, 3.9 ± 2.3 and 2.6 ± 1.5, respectively. No association between ND defined by FTND, HSI or TTF and age was found. In turn, heavy smoking was significantly associated with older age (odds ratio (OR) = 1.72, 95% confidence interval (CI): 1.14-2.59, p = 0.009), and men were more likely than women to be heavy smokers (OR = 1.70, 95% CI: 1.09-2.65, p = 0.018). Chronic comorbidity did not significantly influence ND. An analysis of association of studied polymorphisms with ND showed a borderline association of rs16969968 with CPD (OR = 1.63, 95% CI: 1.09-2.45, p = 0.017). CONCLUSION: Our study showed a low to moderate level of ND in the Kashubians, influenced by age, sex, as well as the CHRNA5 rs16969968 variant.

Association between genetic variants on chromosome 15q25 locus and several nicotine dependence traits in Polish population: a case-control study.

Tobacco smoking continues to be a leading cause of disease and mortality. Recent research has confirmed the important role of nicotinic acetylcholine receptor (nAChR) gene cluster on chromosome 15q 24-25 in nicotine dependence and smoking. In this study we tested the association of smoking initiation, age at onset of daily smoking, and heaviness of smoking with five single nucleotide polymorphisms (SNPs) within the CHRNA5-CHRNA3-CHRNB4 cluster. The group of 389 adult subjects of European ancestry from the north of Poland, including 212 ever (140 current and 72 former) and 177 never smokers with mean age 49.26, was genotyped for rs16969868, rs1051730, rs588765, rs6495308, and rs578776 polymorphisms. Distributions of genotypes for rs16969868 and rs1051730 were identical so they were analyzed together. Further analysis revealed the association between rs16969868-1051730 (OR = 2.66; 95% CI: 1.30-5.42) and number of cigarettes smoked per day (CPD) with heaviness of nicotine addiction measured by the Fagerström Test for Nicotine Dependence (FTND) (OR = 2.60; 95% CI: 1.24-5.43). No association between these polymorphisms and other phenotypes was found. Similarly, the association between rs588765, rs6495308, rs578776, and analyzed phenotypes was not confirmed. This study provides strong evidence for the role of the CHRNA5-CHRNA3-CHRNB4 cluster in heaviness of nicotine addiction.

Respiratory bronchiolitis-interstitial lung disease.

Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is a rare, mild inflammatory pulmonary disorder that occurs almost exclusively in current or former heavy smokers, usually between the third and sixth decades, most likely with no gender predilection. The onset is usually insidious with exertional dyspnea and persistent cough, which may be non-productive, developing over a course of weeks or months. RB-ILD may also be diagnosed in asymptomatic patients with functional impairment and chest radiograph or high-resolution computed tomography (HRCT) abnormalities. Histologically, RB-ILD is characterized by the accumulation of yellow-brown pigmented macrophages within the lumens of respiratory bronchioles and alveolar ducts, associated with a patchy submucosal and peribronchiolar chronic inflammation. Common findings also include mild bronchiolar and peribronchiolar alveolar fibrosis that expands contiguous alveolar septa and leads to architectural distortion as well as centrilobular emphysema. Chest radiographs in patients with RB-ILD typically show fine reticulonodular interstitial opacities, while on HRCT central and peripheral bronchial wall thickening, centrilobular nodules, and ground-glass opacities associated with upper lobe centrilobular emphysema are most frequently reported. Pulmonary function testing may be normal but usually demonstrates mixed, predominantly obstructive abnormalities, often combined with hyperinflation and usually associated with a mild to moderate reduction in carbon monoxide diffusion capacity (DLco). The course of RB-ILD is heterogeneous. Some patients respond favorably to corticosteroids and/or smoking cessation, but often there is no functional improvement and the disease progresses despite smoking cessation and treatment.

The many faces of tobacco use among women.

Smoking is still considered to be mainly a male problem. However, it is estimated that there are approximately 250 million women worldwide who smoke cigarettes and millions more women who use smokeless tobacco products. This article addresses the many facets of tobacco use among women. The aim of the paper is to increase recognition among clinicians and researchers of the specific characteristics of female tobacco use. Together with providing epidemiological data on the distribution of tobacco use among women and data from population-based analyses on sociocultural factors that influence it, the article presents tobacco use during pregnancy as a particularly important public health problem. Further, the article points out sex-related differences (ie, physiological, psychological, or behavioral) between male and female tobacco use. A special focus is on the important role of ovarian hormones. Adverse effects of tobacco use to women and their children as well as tobacco-related morbidities and comorbidities are presented, and women's greater susceptibility to tobacco constituents as compared to men is stressed. Awareness of these differences can contribute to improvement of the effectiveness of smoking cessation programs addressed both to the specific female population and to an individual smoking woman.