Characteristics of Interstitial Pneumonia With Autoimmune Features (IPAF): Protocol for a Multicenter Prospective Study.

BACKGROUND: "Interstitial lung disease" (ILD) is a broad term encompassing diseases of different backgrounds. "Interstitial pneumonia with autoimmune features" (IPAF) is a recent term that implies the presence of autoimmunity. OBJECTIVE: This study aims to determine the characteristics of Polish patients with IPAF, compare them with patients with other interstitial pneumonias, and search for the prognostic and diagnostic biomarkers of IPAF in serum and bronchoalveolar lavage fluid (BALF). METHODS: This multicenter prospective study plans to recruit 240 participants divided into 1 study group and 2 control groups. Biological fluid samples will be collected according to Polish Respiratory Society management guidelines and stored at -80°C for further tests. Prospective 5-year observations of 60 newly diagnosed individuals are planned. The study will be divided into subsections. First, we plan to characterize Polish patients with IPAF (study group) against their peers with other ILDs (2 control groups). Control group 1 will comprise patients with idiopathic ILDs, including mainly idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. Control group 2 will comprise patients with connective tissue disease-associated interstitial lung diseases, such as rheumatoid arthritis, systemic sclerosis, polymyositis, dermatomyositis, Sjögren's syndrome, mixed connective tissue disease, and systemic lupus erythematosus. Radiological and functional parameters will be analyzed. Patients will be compared in terms of high-resolution computed tomography results, the 6-minute walking test performance, and pulmonary function test parameters. The diagnosis of IPAF will be reassessed on a regular basis through multidisciplinary discussion in order to determine its clinical stability. In the laboratory arm, inflammation and fibrosis pathways will be assessed. Cytokine levels (interleukin 8, transforming growth factor beta 1, chemokine C-C motif ligand [CXCL]18, CXCL1, surfactant protein [SP]-A, SP-D, Krebs von den Lungen-6 protein, and chitinase 1) will be measured in serum and BALF. A comparative analysis of serum and BALF cytokine levels will be performed in order to establish potential differences between systemic and local inflammatory pathways. In the quality of life (QoL) arm of the study, dyspnea and cough and their impact on various aspects of the QoL will be assessed. Depression and anxiety will be measured with the Hospital Anxiety and Depression Modified Scale and the 9-item Patient Health Questionnaire, and potential correlations with symptom prevalence will be assessed. RESULTS: This study will start recruiting patients to phase 1 in October 2023. The final results will be available in 2028. We plan to publish preliminary results after 2-3 years from the start of phase 1. CONCLUSIONS: This study will be a step toward a better understanding of IPAF etiopathogenesis and outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/44802.

Are There Differences in Inflammatory and Fibrotic Pathways between IPAF, CTD-ILDs, and IIPs? A Single-Center Pilot Study.

In this pilot study, we aim to determine differences in pathogenetic pathways between interstitial pneumonia with autoimmune features (IPAF), connective-tissue-disease-associated interstitial lung diseases (CTD-ILDs), and idiopathic interstitial pneumonias (IIPs). Forty participants were recruited: 9 with IPAF, 15 with CTD-ILDs, and 16 with IIPs. Concentration of transforming growth factor beta (TGF-ß1), surfactant proteins A and D (SP-A, SP-D), interleukin 8 (IL-8), and chemokine 1 (CXCL1) were assessed with ELISA assay in bronchoalveolar lavage (BAL) fluid. We revealed that IL-8 and TGF-ß1 concentrations were significantly lower in the IPAF group than in the CTD-ILD group (p = 0.008 and p = 0.019, respectively), but similar to the concentrations in the IIP group. There were significant correlations of IL-8 (rs = 0.46; p = 0.003) and CXCL1 (rs = 0.52; p = 0.001) and BAL total cell count (TCC). A multivariate regression model revealed that IL-8 (ß = 0.32; p = 0.037) and CXCL1 (ß = 0.45; p = 0.004) are significant predictors of BAL TCC. We revealed that IL-8 and TGF-ß1 BAL concentrations vary in patients with different ILDs and found that IL-8 is a predictor of BAL TCC in IPAF. However, this needs to be confirmed in a multicenter cooperative study (ClinicalTrials.gov Identifier: NCT03870828).

Patterns of lung fibrosis in patients with interstitial pneumonia with autoimmune features and connective tissue diseases-associated interstitial lung disease-a narrative review.

BACKGROUND AND OBJECTIVE: Interstitial pneumonia with autoimmune features (IPAF) was defined in 2015 as a research statement of European Respiratory Society and American Thoracic Society. Connective tissue diseases (CTDs) manifest in the respiratory tract, the main manifestation being interstitial lung disease, which contributes to morbidity and mortality. This poses numerous clinical challenges and is a substantial burden on healthcare systems around the world. The objective of this narrative review was to provide readers with a comprehensive and extensive overview of such manifestations in the respiratory system, analysis of prevalence of specific manifestations in the lung and to characterize population of patients with IPAF. METHODS: We reviewed the current state of knowledge on radiological findings in interstitial lung diseases in course of convective tissue diseases and IPAF, a narrative review of PubMed database using Advanced Search Builder was performed. The search was conducted from 15.07.2021 to 03.04.2022. A total of 655 articles in English were reviewed. KEY CONTENT AND FINDINGS: Similarities and differences between interstitial pneumonia in course of well-established CTDs and IPAF are discussed with special emphasis on required future research areas. Manifestations of CTDs in the respiratory system are overviewed, with the emphasis on interstitial lung disease, as despite clinical similarities of various connective tissue diseases, there is variability in their presentation in the respiratory system, radiological patterns and clinical outcomes. We would also like to draw readers' attention to clinical significance of interstitial lung abnormality both in the context of CTDs and lack of underlying autoimmune disorders. CONCLUSIONS: There is need for prospective cohort studies regarding the natural course of IPAF, its clinical stability and its manifestations in the respiratory system. Prospective studies are also required to evaluate diagnostic and prognostic factors of IPAF. Interstitial lung disease associated with CTDs (CTD-ILD) is a significant factor impacting clinical outcomes and patient prognosis, therefore its diagnostic work-up is best performed by an experienced multidisciplinary team and with use of procedures of high diagnostic yield.

Review: Serum Biomarkers of Lung Fibrosis in Interstitial Pneumonia with Autoimmune Features-What Do We Already Know?

Interstitial pneumonia with autoimmune features (IPAF) belongs to a group of diseases called interstitial lung diseases (ILDs), which are disorders of a varied prognosis and course. Finding sufficiently specific and sensitive biomarkers would enable the progression to be predicted, the natural history to be monitored and patients to be stratified according to their treatment. To assess the significance of pulmonary fibrosis biomarkers studied thus far, we searched the PubMed, Medline and Cochrane Library databases for papers published between January 2015 and June 2021. We focused on circulating biomarkers. A primary review of the databases identified 38 articles of potential interest. Overall, seven articles fulfilled the inclusion criteria. This review aims to assess the diagnostic and prognostic value of molecules such as KL-6, SP-A, SP-D, circulating fibrocytes, CCL2, CXCL13, CXCL9, CXCL10 and CXCL11. All of these biomarkers have previously been studied in idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). IPAF is a disorder of a heterogeneous nature. It explains the lack of coherent observations in terms of correlations with functional parameters. There is still no meta-analysis of pulmonary fibrosis biomarkers in IPAF. This is mainly due to the heterogeneity of the methodology and groups analysed in the research. More research in this area is needed.

Inhalation Techniques Used in Patients with Respiratory Failure Treated with Noninvasive Mechanical Ventilation.

The administration of aerosolized medication is a basic therapy for patients with numerous respiratory tract diseases, including obstructive airway diseases (OADs), cystic fibrosis (CF), and infectious airway diseases. The management and care for patients requiring mechanical ventilation remains one of the greatest challenges for medical practitioners, both in intensive care units (ICUs) and pulmonology wards. Aerosol therapy is often necessary for patients receiving noninvasive ventilation (NIV), which may be stopped for the time of drug delivery and administered through a metered-dose inhaler or nebulizer in the traditional way. However, in most severe cases, this may result in rapid deterioration of the patient's clinical condition. Unfortunately, only limited number of original well-planned studies addressed this problem. Due to inconsistent information coming from small studies, there is a need for more precise data coming from large prospective real life studies on inhalation techniques in patients receiving NIV.

Novel method of noninvasive ventilation supported therapeutic lavage in pulmonary alveolar proteinosis proves to relieve dyspnea, normalize pulmonary function test results and recover exercise capacity: a short communication.

Whole lung lavage (WLL) under general anesthesia with a double-lumen endobronchial intubation has remained standard treatment option for pulmonary alveolar proteinosis (PAP) for over fifty years now. To the best of our knowledge, this is the first description of noninvasive ventilation (NIV) as an innovative alternative, which enables safe and effective treatment. NIV support enabled cost-effective lavage of the most affected segments and resulted in restoration and long-term maintenance of exercise capacity and diffusion, without WLL related hypoxaemia, volume overload, intubation, or mechanical ventilation related complications. The study presents all details of performed procedure, including anesthesia, NIV technique and bronchoscopy, therefore this may be easily implemented into clinical practice at other centers conducting PAP treatment. We assume that presented technique of therapeutic lung lavage (TLL) with NIV support may be considered a novel PAP treatment method, however, target population who will benefit the most from such therapy modification must be assessed in large scale prospective trials.

Influence of noninvasive ventilation on clinical status, dyspnea sensation and subsequent copd diagnosis.

Chronic obstructive lung disease (COPD) is a common life-threatening disease characterized by exposure to tobacco smoke, dyspnea and persistent lower airway obstruction coexistence of COPD and chronic heart failure (HF) may present a considerable challenge during both diagnostic and therapeutic processes. Herein, we report an elderly, obese male, an ex-smoker, suffering from both COPD and HF, and treated according to the applied guidelines for 15 years. On admission to hospital, the patient was diagnosed and treated for severe type 2 respiratory failure. The patient's COPD diagnosis was questioned at first, but then reconsidered after treatment described below. Noninvasive ventilation (NIV) improved the patient's clinical condition and reduced his dyspnea sensation. As a consequence, during check-ups, spirometry maneuvers could have been performed properly, revealing the underlying bronchial obstruction, which had been beforehand concealed by debilitation of respiratory muscles and decreased lung tissue compliance in a patient with chronic HF. Conclusion: NIV application in a patient with type 2 respiratory failure may significantly improve one's clinical condition, reduce dyspnea sensation and help establish an accurate diagnosis.

[Profile of adults suffering from COPD in Poland].

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is one of the most common chronic diseases in adults. It is estimated, that in Poland around two million people suffer from COPD. THE AIM: The aim of this study, was to characterize population of patients with COPD in Poland. MATERIAL AND METHODS: The study, established and coordinated by the Polish Respiratory Society, included a representative sample of 500 GPs where were asked to fill questionnaires on diagnosis and treatment of their COPD patients. The questions dealt with disease history and clinical presentation, COPD severity stage, diagnostic and therapeutic procedures. RESULTS: Altogether 298 physicians (59.6% of invited) provided information about 2756 COPD patients aged 61.6 ± 11.1 years (36.3% were women). According to GOLD recommendations 16.6% of patients had mild, 57.0% moderate, 18.6% severe and 2.1% very severe COPD. Smoking history was declared by 97.8% of respondents. 51.4% of COPD patients had continued smoking. Over the last year Ambulance Service intervened in 19.7% of patients and 29.1% of respondents required hospital treatment of COPD. Among more than 80% of patients, doctor diagnosed limitation in exercise tolerance, and shortness of breath at rest, and in approximately 60% of the respondents were presented productive cough, weakened vesicular murmur and prolonged phase of exhalation. CONCLUSIONS: Despite the diagnosis, more than half of men and women had continued smoking. The number of hospitalizations and emergency intervention positively correlated with the severity of the disease. The survey results emphasize the urgent need for health education in patients with COPD.

[Exacerbations in perimenstrual asthma. Clinical significance of peripheral blood eosinophilia and BMI]. / Zaostrzenia w astmie okolomiesiaczkowej. Znaczenie kliniczne eozynofilii w krwi obwodowej i BMI.

INTRODUCTION: Asthma is a heterogeneous disease characterized by lower airways' obstruction, caused by various factors. There are many asthma phenotypes. Lately, perimenstrual asthma (PMA) with a pattern of exacerbations before and during menstruation as well as obesity associated asthma have been a subject of particular scientific and clinical interest. MATERIAL AND METHODS: 30 women were qualified for this three-arm case-control study(women with a pattern of asthma exacerbations in the perimenstrual period, women with asthma but no perimenstrual exacerbations, healthy control group). All patients performed spirometry and assessed disease control using specific questionnaires. Peripheral blood counts with smear were also performed. RESULTS: PMA patients differ in a statistically significant way in respect of anthropometric measurements such as BMI: in PMA group 25.8±1.8; in non-PMA asthmatics 23.9 ±2.2; healthy control 23.1±1.5; p=0.018) and spirometry results (FEV1 [%]: 85.1 (36.3-113.0); in PMA asthmatics, 93.1 (81,6-109,7), in nonPMA group, p<0.05; 105.4 (108,3-119,0) in healthy control and Tiffeneau index [%]: 70.1 (41.2-98.1); in PMA vs 83.5 (59.6-94.4); in non-PMA asthmatics 93.1(81,8-97,5) in healthy control p<0.05; ). PMA asthmatics also complain of poorer disease control than non-PMA asthmatics. There were no differences in peripheral blood eosinophilia or CRP between studied groups, p>0.05). CONCLUSIONS: Asthma exacerbations are not associated with the effect of peripheral blood eosinophilia. Women with greater BMI are more predisposed to perimenstrual asthma.

My night on call in Poland.

I am a young doctor who graduated from the Medical University of Silesia in 2014. After 13 months of postgraduate training, passing a state examination and successful completion of the admission process I made a decision to specialise in Respiratory Medicine. I started working in a large clinical hospital that provides junior doctors with excellent opportunities for training and career development. The respiratory unit is highly specialised and deals with sleep-related medical problems, interstitial lung diseases and respiratory failure, which may be treated using noninvasive mechanical ventilation. Along with my training in respiratory medicine I decided to start working as an emergency room doctor in a different hospital, in order to improve my skills in treating life-threatening conditions.