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Abstract Background Pulmonary lymphangiomatosis (PL) is an ultrarare disease characterized by diffuse infiltration of the lung, pleura and/or mediastinum by abnormal lymphatic proliferation. Consented diagnostic or treatment approaches are not established. We therefore aimed to collect data on diagnostics and treatments in a cohort of patients with PL from a tertiary center for rare lung diseases. Methods Clinical, radiological and outcome data from PL patients were collected retrospectively. Results 12 patients were diagnosed between 1996 and 2022 in our center. PL was diagnosed more commonly in female (58%), never smokers (75%) and younger patients (mean age 42 years). Main clinical symptoms comprised haem- and chyloptysis (58%) and dyspnea on exertion (83%). Pulmonary function was mostly restrictive (mean VC 59%) with impaired DLCO (mean 65%). Radiological assessment mainly showed mediastinal involvement (83%), and pleural effusion (67%), pleural thickening (67%) and bronchial wall thickening (67%) while interstitial changes were rare. Diagnosis was confirmed by surgical or transbronchial cryobiopsy. 8 patients were treated with sirolimus, 3 of these combined with a surgical intervention and in one case surgical intervention was necessary 9 months after initiation of sirolimus. Clinical and radiological improvement was demonstrated for all patients treated with sirolimus. 1 patient received a lung transplant due disease progression. Survival rates were 90% after a mean follow up of at least 3 months. Conclusion This case series illustrates the variability of the clinical presentation of PL. Among our patients, those treated with sirolimus showed significant clinical, functional and radiological improvement. However, further investigation is needed to understand the pathogenesis of lymphangiomatosis in order to establish therapeutic approaches.

The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis.The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally.This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year.All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines.Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10–80% in the remaining 5 countries).The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3−7) in the overall cohort and 6 (4−8) among patients with a final outcome).For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13−23) (in days 553 (385–678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30−90) days for the whole cohort and 60 (30−100) for patients with a final outcome and, respectively, of 55 (30−90) and 60 (30−90) days for culture conversion.Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.

Analysis of inflammatory biomarkers and lymphocytes during the treatment of tuberculosis (TB) could yield findings that influence the routine clinical practice and use of new anti-TB drugs. This study aimed to evaluate whether the selected biomarkers—soluble intercellular adhesion molecule type 1, soluble urokinase-type plasminogen activator receptor (suPAR), and C-reactive protein (CRP)—and T-cell subpopulations are useful for predicting culture conversion, treatment outcomes, and the extent of radiological lesions (calculated using X-ray score) in patients with drug-sensitive pulmonary TB. This study included 62 patients with drug-sensitive pulmonary TB. CRP and suPAR levels significantly decreased after 1 month of treatment. Before treatment initiation, CRP and suPAR levels were significantly higher in patients without culture conversion; however, none of the selected host biomarkers appeared to significantly influence the conversion status or treatment outcomes. Some lymphocyte subpopulations were correlated with X-ray scores before TB treatment initiation, but lung destruction, as determined using X-ray scores, showed the highest correlation with the baseline CRP value. We conclude that selected host biomarkers have a very limited role in predicting TB treatment outcomes and culture conversion and do not appear to be superior to CRP in monitoring TB treatment.

Abstract Background Severe non-allergic eosinophilic asthma (SNEA) is a rare asthma phenotype associated with severe clinical course, frequent exacerbations, and resistance to therapy, including high steroid doses. The key feature is type 2 inflammation with predominant airway eosinophilia. Eosinophil maturation, activation, survivability, and recruitment are mainly induced by interleukin (IL)-3, IL-5 and granulocyte–macrophage colony-stimulating factor (GM-CSF) through their receptors on eosinophil surface and related with integrins activation states. The aim of the study was to estimate the expression of eosinophil β chain-signaling cytokines receptors, outer-membrane integrins, and serum-derived type 2 inflammation biomarkers in SNEA. Methods We examined 8 stable SNEA patients with high inhaled steroid doses, 12 steroid-free patients with non-severe allergic asthma (AA), 12 healthy subjects (HS). Blood eosinophils were isolated using Ficol gradient centrifugation and magnetic separation. Eosinophils were lysed, and mRNA was isolated. Gene expressions of IL-5Rα, IL-3Rα, GM-CSFRα, and α4β1, αMβ2 integrins were analyzed using quantitative real-time reverse transcription polymerase chain reaction. Type 2 inflammation activity was evaluated measuring exhaled nitric oxide concentration (FeNO) collected with the electrochemical sensing device. Serum IL-5, IL-3, GM-CSF, periostin, chemokine ligand (CCL) 17 and eotaxin concentrations were assessed by enzyme-linked immunosorbent assay. Results Eosinophils from SNEA patients demonstrated significantly increased gene expression of IL-3Rα, IL-5Rα and GM-CSFRα as well as α4, β1 and αM integrin subunits compared with the AA group. The highest IL-5 serum concentration was in the SNEA group; it significantly differed compared with AA and HS. GM-CSF serum levels were similar in the SNEA and AA groups and were significantly lower in the HS group. No differences in serum IL-3 concentration were found among all groups. Furthermore, serum levels of eotaxin, CCL17 and FeNO, but not periostin, differed in all groups, with the highest levels in SNEA patients. Conclusions Eosinophil demonstrated higher expression of IL-3, IL-5, GM-CSF α-chain receptors and α4, β1, αM integrins subunits in SNEA compared with the AA group. Additionally, SNEA patients had increased serum levels of IL-5, eotaxin and CCL-17. Trial registration ClinicalTrials.gov Identifier NCT03388359.

Eisenmenger syndrome (ES) is the most severe form of pulmonary arterial hypertension (PAH) associated with congenital heart disease. It is an extremely devastating condition with a serious impact on patients' life. Classical therapy of ES remains directed to avoid complications, such as erythrocytosis, treatment of congestive heart failure, prevention of infection, and secondary haematological abnormalities such as iron deficiency and coagulation disorders. However, the only effective treatment is heart–lung transplantation; still, morbidity and mortality after transplantation remain substantially high. Furthermore, waiting lists for heart–lung transplantation are long. Recent studies examining the use of advanced medical treatment in patients with ES have shown that it may have beneficial effects in patients with ES; however, additional studies need to be done to confirm its efficacy and appropriate clinical use. A 41-year-old female admitted to the Hospital of Lithuanian University of Health Sciences due to progressive dyspnea on minimal effort, heart failure symptoms leading to NYHA functional class III-IV. After clinical and instrumental investigations, ES secondary to unrepaired patent ductus arteriosus with severe PAH was diagnosed. Treatment with sildenafil was initiated together with the standard pharmacological therapy, and the patient was added to the waiting list for the heart and lung transplantation. After 24 months of stable condition, her clinical status deteriorated, and combination therapy (sildenafil and ambrisentan) was initiated. Clinical symptoms and exercise capacity improved, and she has been stable for 4 years thereafter. Our experience of the management of an adult patient with ES showed the benefits of treatment with advanced therapy with pulmonary vasodilators that improved the patient's quality of life and delayed the need for heart and lung transplantation.

The bronchial epithelium has continuous contact with environmental agents initiating and maintaining airway type 2 inflammation in asthma. However, there is a lack of data on whether reduced airway eosinophilic inflammation can affect the production of epithelial-derived mediators, such as interleukin-25 (IL-25) and thymic stromal lymphopoietin (TSLP). The aim of this study was to investigate the changes in serum levels of IL-25 and TSLP after a single dose of mepolizumab, a humanized monoclonal antibody to interleukin-5 (IL-5), in patients with severe non-allergic eosinophilic asthma (SNEA). We examined 9 SNEA patients before and four weeks after administration of 100 mg mepolizumab subcutaneously. The fractional exhaled nitric oxide (FeNO) level was analysed using an electrochemical assay (NIOX VERO®, Circassia, UK). Serum IL-25 and TSLP levels were measured by ELISA. Four weeks after the single dose of mepolizumab, blood eosinophil count significantly decreased from 0.55 ± 0.20 × 109/l to 0.14 ± 0.04 × 109/l (p=0.01) and FEV1 increased from 2.1 ± 0.5 l (65.4 ± 8.8% of predicted) to 2.6 ± 0.4 l (76.4 ± 9.1% of predicted) (p=0.04), while FeNO level has not changed (32.3 ± 8.4 vs 42.9 ± 12.6 ppb). Serum IL-25 level significantly decreased from 48.0 ± 17.2 pg/mL to 34.8 ± 17.1 pg/mL (p=0.02) with same tendency in TSLP level: from 359.8 ± 71.3 pg/mL to 275.6 ± 47.8 pg/mL (p=0.02). It has also been noticed a significant relation between changes in the blood eosinophil count and serum IL-25 level (r = 0.81, p=0.008), as well as between changes in serum IL-25 and TSLP levels (r = 0.93, p=0.004) after a single dose of mepolizumab. Thus, anti-IL-5 treatment with mepolizumab might diminish the production of bronchial epithelial-derived cytokines IL-25 and TSLP in patients with SNEA which is potentially related to reduced eosinophilic inflammation. This trial is registered in ClinicalTrial.gov with identifier NCT03388359.