Pseudomonas aeruginosa in chronic lung disease: untangling the dysregulated host immune response.

Pseudomonas aeruginosa is a highly adaptable opportunistic pathogen capable of exploiting barriers and immune defects to cause chronic lung infections in conditions such as cystic fibrosis. In these contexts, host immune responses are ineffective at clearing persistent bacterial infection, instead driving a cycle of inflammatory lung damage. This review outlines key components of the host immune response to chronic P. aeruginosa infection within the lung, beginning with initial pathogen recognition, followed by a robust yet maladaptive innate immune response, and an ineffective adaptive immune response that propagates lung damage while permitting bacterial persistence. Untangling the interplay between host immunity and chronic P. aeruginosa infection will allow for the development and refinement of strategies to modulate immune-associated lung damage and potentiate the immune system to combat chronic infection more effectively.

Why do a lung biopsy for benign lesions?

BACKGROUND: Transthoracic needle biopsy of lung lesions is a well-established procedure for the diagnosis of lung lesions. The literature focuses on the diagnosis of malignant lesions with an often reported accuracy rate of more than 90%. Experience showed that biopsy can identify sometimes incidentally, also benign lesions. There are many reasons why a biopsy is performed for a "benign lesion." First of all, it may be an unexpected diagnosis, as some benign pathologies may have misleading presentations, that are very similar to lung cancer, otherwise the reason is only to make a diagnosis of exclusion, which leads to the benign pathology already being considered in the differential diagnosis. METHODS: This study was designed as a retrospective single-center study. We selected from our database all the lung biopsies performed under CT guidance, from 2015 to 2019 and retrospectively analysed the histological data. We selected only benign lesions describing the imaging feature and differential diagnosis with lung malignancy. RESULTS: In our patient population, among the 969 of them that underwent biopsy, we identified 93 benign lesions (10%). Hamartomas, granulomas, slow-resolving pneumonia and cryptogenic organizing pneumonia are the pathologies that most frequently can misinterpratedas lung cancer. CONCLUSIONS: In this brief report we want to show the percentage and type of benign lesions that are found in our lung trans-thoracic biopsy population. Among these, we identified the three most frequent benign lesions that most frequently enter the differential diagnosis with lung malignant lesions describing the classic and atypical imaging findings.

Advanced Delivery Strategies of Nintedanib for Lung Disorders and Beyond: A Comprehensive Review.

Nintedanib, a primary treatment for lung fibrosis, has gathered substantial attention due to its multifaceted potential. A tyrosine kinase inhibitor, nintedanib, inhibits multiple signalling receptors, including endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR) and ultimately inhibits fibroblast proliferation and differentiation. Therefore, nintedanib has been studied widely for other ailments like cancers and hepatic fibrosis, apart from lung disorders. Commercially, nintedanib is available as soft gelatin capsules for treatment against idiopathic pulmonary fibrosis. Since it has very low oral bioavailability (4.7%), high doses of a drug, such as 100-150 mg, are administered, which can cause problems of gastrointestinal irritation and hepatotoxicity. The article begins with exploring the mechanism of action of nintedanib, elucidating its complex interactions within cellular pathways that govern fibrotic processes. It also emphasizes the pharmacokinetics of nintedanib, clinical trial insights, and the limitations of conventional formulations. The article mainly focuses on the emerging landscape of nanoparticle-based carriers such as hybrid liposome-exosome, nano liquid crystals, discoidal polymeric, and magnetic systems, offering promising avenues to optimize drug targeting, address its efficacy issues and minimise adverse effects. However, none of these delivery systems are commercialised, and further research is required to ensure safety and effectiveness in clinical settings. Yet, as research progresses, these advanced delivery systems promise to revolutionise the treatment landscape for various fibrotic disorders and cancers, potentially improving patient outcomes and quality of life.

Lower Income, Smoking, Cardiopulmonary Comorbidities, and Higher Symptom Burden Influence the Occurrence of Cough in Patients Receiving Chemotherapy.

OBJECTIVES: To identify subgroups of patients with distinct cough occurrence profiles and evaluate for differences among these subgroups. SAMPLE & SETTING: Outpatients receiving chemotherapy (N = 1,338) completed questionnaires six times over two chemotherapy cycles. METHODS & VARIABLES: Occurrence of cough was assessed using the Memorial Symptom Assessment Scale. Latent class analysis was used to identify subgroups with distinct cough occurrence profiles. Parametric and nonparametric tests were used to evaluate for differences. RESULTS: Four distinct cough profiles were identified (None, Decreasing, Increasing, and High). Risk factors associated with membership in the High class included lower annual household income; history of smoking; self-reported diagnoses of lung disease, heart disease, and back pain; and having lung cancer. IMPLICATIONS FOR NURSING: Clinicians need to assess all patients with cancer for cough and provide targeted interventions.

Breath of fresh air: Investigating the link between AGEs, sRAGE, and lung diseases.

Advanced glycation end products (AGEs) are compounds formed via non-enzymatic reactions between reducing sugars and amino acids or proteins. AGEs can accumulate in various tissues and organs and have been implicated in the development and progression of various diseases, including lung diseases. The receptor of advanced glycation end products (RAGE) is a receptor that can bind to advanced AGEs and induce several cellular processes such as inflammation and oxidative stress. Several studies have shown that both AGEs and RAGE play a role in the pathogenesis of lung diseases, such as chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, cystic fibrosis, and acute lung injury. Moreover, the soluble form of the receptor for advanced glycation end products (sRAGE) has demonstrated its ability to function as a decoy receptor, possessing beneficial characteristics such as anti-inflammatory, antioxidant, and anti-fibrotic properties. These qualities make it an encouraging focus for therapeutic intervention in managing pulmonary disorders. This review highlights the current understanding of the roles of AGEs and (s)RAGE in pulmonary diseases and their potential as biomarkers and therapeutic targets for preventing and treating these pathologies.

Undercover lung damage in pediatrics - a hot spot in morbidity caused by collagenoses.

Connective tissue represents the support matrix and the connection between tissues and organs. In its composition, collagen, the major structural protein, is the main component of the skin, bones, tendons and ligaments. Especially at the pediatric age, its damage in the context of pathologies such as systemic lupus erythematosus, scleroderma or dermatomyositis can have a significant negative impact on the development and optimal functioning of the body. The consequences can extend to various structures (e.g., joints, skin, eyes, lungs, heart, kidneys). Of these, we retain and reveal later in our manuscript, mainly the respiratory involvement. Manifested in various forms that can damage the chest wall, pleura, interstitium or vascularization, lung damage in pediatric systemic inflammatory diseases is underdeveloped in the literature compared to that described in adults. Under the threat of severe evolution, sometimes rapidly progressive and leading to death, it is necessary to increase the popularization of information aimed at physiopathological triggering and maintenance mechanisms, diagnostic means, and therapeutic directions among medical specialists. In addition, we emphasize the need for interdisciplinary collaboration, especially between pediatricians, rheumatologists, infectious disease specialists, pulmonologists, and immunologists. Through our narrative review we aimed to bring up to date, in a concise and easy to assimilate, general principles regarding the pulmonary impact of collagenoses using the most recent articles published in international libraries, duplicated by previous articles, of reference for the targeted pathologies.

Placental Transmogrification of the Lung Presenting as Cystic-Solid Mass: A Case Report.

The gradually progressive solitary cystic-solid mass of chest CT scans is highly suggestive of lung cancer. We report a case of a 29-year-old woman with a persistent cystic-solid lesion in the right upper lobe. A chest CT scan showed a 35 mm × 44 mm × 51 mm focal cystic-solid mass in the anterior segment of the right upper lobe. The size of lesion had increased over 3 years, especially for the solid component. The right upper lobe pneumonectomy was performed. Postoperative pathological examination showed placental transmogrification of the lung, which is a rare cause of pulmonary cystic lesion.

Longitudinal lung function trajectories in response to azithromycin therapy for chronic lung disease in children with HIV infection: a secondary analysis of the BREATHE trial.

BACKGROUND: Chronic lung disease (CLD) is common among children with HIV (CWH) including in those taking antiretroviral therapy (ART). Azithromycin has both antimicrobial and anti-inflammatory effects and has been effective in improving lung function in a variety of lung diseases. We investigated lung function trajectories among CWH with CLD on ART enrolled in a randomized controlled trial of adjuvant azithromycin. We also investigated factors that modified the effect of azithromycin on lung function. METHODS: The study used data from a double-blinded placebo-controlled trial conducted in Malawi and Zimbabwe of 48 weeks on azithromycin (BREATHE: ClinicalTrials.gov NCT02426112) among CWH aged 6 to 19 years taking ART for at least six months who had a forced expiratory volume in one second (FEV1) z-score <-1.0. Participants had a further follow-up period of 24 weeks after intervention cessation. FEV1, forced vital capacity (FVC) and FEV1/FVC were measured at baseline, 24, 48 and 72-weeks and z-scores values calculated. Generalized estimating equations (GEE) models were used to determine the mean effect of azithromycin on lung-function z-scores at each follow-up time point. RESULTS: Overall, 347 adolescents (51% male, median age 15 years) were randomized to azithromycin or placebo. The median duration on ART was 6.2 (interquartile range: 3.8-8.6) years and 56.2% had an HIV viral load < 1000copies/ml at baseline. At baseline, the mean FEV1 z-score was - 2.0 (0.7) with 44.7% (n = 155) having an FEV1 z-score <-2, and 10.1% had microbiological evidence of azithromycin resistance. In both trial arms, FEV1 and FVC z-scores improved by 24 weeks but appeared to decline thereafter. The adjusted overall mean difference in FEV1 z-score between the azithromycin and placebo arms was 0.004 [-0.08, 0.09] suggesting no azithromycin effect and this was similar for other lung function parameters. There was no evidence of interaction between azithromycin effect and baseline age, lung function, azithromycin resistance or HIV viral load. CONCLUSION: There was no observed azithromycin effect on lung function z-scores at any time point suggesting no therapeutic effect on lung function. TRIAL REGISTRATION: ClinicalTrials.gov NCT02426112. First registered on 24/04/2015.

Protected characteristics reported in pulmonary rehabilitation: a scoping review.

BACKGROUND: An individual's characteristics are reported to influence access, completion and outcomes of pulmonary rehabilitation and may contribute to health inequalities. Many countries have policies to promote equity among individuals' characteristics, including the UK Equality Act 2010 which lists nine protected characteristics (age, disability, gender reassignment, marriage and civil partnership, pregnancy and maternity, race, religion or belief, sex and sexual orientation). OBJECTIVES: To describe the extent to which UK Equality Act 2010 protected characteristics have been collected and reported in UK studies and audits of pulmonary rehabilitation. METHODS: A scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines was conducted using five databases. UK studies and audits collecting data on pulmonary rehabilitation from 1 October 2010 (date of Equality Act 2010 inception) were eligible. The protected characteristics collected and how they were reported were extracted. RESULTS: Out of 45 included studies and audits (41 studies and four audits), 98% (k=44) reported age. Sex was reported in 40% (k=18), and 20% (k=9) reported gender with only male and female categories. Half (50%, k=2) of audits reported gender with male, female and transgender categories. Race was reported through ethnicity in 2% (k=1) of studies and 75% (k=3) of audits. No studies or audits explicitly reported disability, but all reported measures indicating disease severity (e.g. forced expiratory volume in 1 s % predicted: 67%, k=30). No studies or audits reported marriage and civil partnership, pregnancy and maternity, religion or belief or sexual orientation. CONCLUSIONS: Protected characteristics are not commonly reported or are inconsistently reported in UK pulmonary rehabilitation studies and audits. Without reporting these characteristics, health inequalities in pulmonary rehabilitation will remain unclear.

[Pulmonary Amyloidosis Observed by Thoracoscopy:Report of a Case].

The case is an 80-year-old woman with Sjögren's syndrome. During the follow-up of multiple pulmonary nodules, an enlarged nodule was observed in the peripheral of the right S3 interlobar region. Fluorodeoxyglucose- positron emission tomography (FDG-PET) showed FDG accumulation only in the S3 nodule, which led to suspicion of primary lung cancer. Because of its difficult location to reach by bronchoscopy, a right lung S3 segmentectomy was performed. Intraoperative findings revealed a hard yellowish- white nodule just below the pleura. Pathological examination showed that the nodule consisted of an acidophilic structureless material, which was positive for Congo red staining and disappeared after permanganate treatment. Based on the above findings, we diagnosed amyloid A( AA)-type amyloidosis. In this case, the nodule was located just below the pleura and we could observe it by thoracoscopy. There have been few reports of thoracoscopic observation of pulmonary amyloidosis, and we report with intraoperative findings.

Late-Onset Noninfectious Pulmonary Complications After Allogeneic Hematopoietic Stem Cell Transplantation: Single-Center Experience.

OBJECTIVES: We aimed to reveal the incidence of lateonset noninfectious pulmonary complications and bronchiolitis obliterans syndrome and risk factors involved in development. MATERIALS AND METHODS: In this cross-sectional study, we retrospectively investigated 745 patients who underwent allogeneic hematopoietic stem cell transplantation in our hospital between January 2000 and December 2020. We evaluated demographic characteristics, comorbidities, and hematopoietic stem cell transplantation characteristics to determine possible risk factors affecting development of lateonset noninfectious pulmonary complications and bronchiolitis obliterans syndrome. RESULTS: Of 745 patients, 8.9% (n = 66) had late-onset noninfectious pulmonary complications. Complications included 38 patients with bronchiolitis obliterans syndrome, 13 with venous thromboembolism, 8 with cryptogenic organizing pneumonia, 5 with pneumothorax, 4 with interstitial lung disease-restrictive graft-versus-host disease, 5 with bronchiectasis, 2 with pneumomediastinum, and 1 with pleural effusion. Patients with and without complications were not significantly differentin terms of smoking history, hematopoietic stem cell transplantation characteristics, and conditioning regimens. Patients with complications had higher busulfan and lower antithymocyte globulin use than those without complications (both P<.05). Patients with complications more commonly had hematopoietic stem cell transplantation from related donors and chronic graft-versus-host disease (P < .05). Patients with bronchiolitis obliterans syndrome had more frequent use of busulfan (P <.05) but less frequent use of total body irradiation (P <.05) and antithymocyte globulin (P <.05) than those without this syndrome. Rate of hematopoietic stem cell transplantation from a related donor (P < .05) and frequency of chronic graftversus-host disease (P < .001) were significantly higher in patients with bronchiolitis obliterans syndrome, presented with bronchiectasis (78.6%), air trapping (67.9%), bronchial wallthickening (53.6%), and mosaic attenuation (39.3%) in thorax computed tomography. Pretransplant spirometry did not predict bronchiolitis obliterans syndrome development. CONCLUSIONS: Determining risk factors for late-onset noninfectious pulmonary complications is needed to aid in prevention and follow-up.

In-silico discovery of common molecular signatures for which SARS-CoV-2 infections and lung diseases stimulate each other, and drug repurposing.

COVID-19 caused by SARS-CoV-2 is a global health issue. It is yet a severe risk factor to the patients, who are also suffering from one or more chronic diseases including different lung diseases. In this study, we explored common molecular signatures for which SARS-CoV-2 infections and different lung diseases stimulate each other, and associated candidate drug molecules. We identified both SARS-CoV-2 infections and different lung diseases (Asthma, Tuberculosis, Cystic Fibrosis, Pneumonia, Emphysema, Bronchitis, IPF, ILD, and COPD) causing top-ranked 11 shared genes (STAT1, TLR4, CXCL10, CCL2, JUN, DDX58, IRF7, ICAM1, MX2, IRF9 and ISG15) as the hub of the shared differentially expressed genes (hub-sDEGs). The gene ontology (GO) and pathway enrichment analyses of hub-sDEGs revealed some crucial common pathogenetic processes of SARS-CoV-2 infections and different lung diseases. The regulatory network analysis of hub-sDEGs detected top-ranked 6 TFs proteins and 6 micro RNAs as the key transcriptional and post-transcriptional regulatory factors of hub-sDEGs, respectively. Then we proposed hub-sDEGs guided top-ranked three repurposable drug molecules (Entrectinib, Imatinib, and Nilotinib), for the treatment against COVID-19 with different lung diseases. This recommendation is based on the results obtained from molecular docking analysis using the AutoDock Vina and GLIDE module of Schrödinger. The selected drug molecules were optimized through density functional theory (DFT) and observing their good chemical stability. Finally, we explored the binding stability of the highest-ranked receptor protein RELA with top-ordered three drugs (Entrectinib, Imatinib, and Nilotinib) through 100 ns molecular dynamic (MD) simulations with YASARA and Desmond module of Schrödinger and observed their consistent performance. Therefore, the findings of this study might be useful resources for the diagnosis and therapies of COVID-19 patients who are also suffering from one or more lung diseases.

Pulmonary manifestations of VEXAS syndrome with acute interstitial pneumonia and diffuse alveolar hemorrhage: a case report and literature review.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an emerging adult-onset systemic autoinflammatory disorder affecting multiple organ systems. While lung involvement is common in this syndrome, literature regarding specific patterns is sparse. In this report, we present a case description of a patient with VEXAS syndrome who presented at the emergency department on two separate occasions with acute interstitial pneumonia (AIP) and diffuse alveolar hemorrhage (DAH). A literature review with a comparison of our observed findings to the general findings of VEXAS syndrome, AIP, and DAH is provided. This report underscores the rarity of specific pulmonary manifestations associated with VEXAS syndrome, contributing valuable insight to the limited literature available on this topic.

The ten-year evaluation of clinical characteristics in congenital lung anomaly in pediatrics; a retrospective study in North of Iran.

INTRODUCTION: Congenital lung anomalies (CLA) are a group of anomalies, including congenital cystic adenomatoid malformation (CCAM), bronchopulmonary sequestrations (BPS), congenital lobar emphysema (CLE), and bronchogenic cysts (BC). The prevalence of these rare anomalies has risen in recent years, according to various population-based studies due to advances in fetal ultrasound technology. METHOD: This retrospective study examines the diagnosis of CLA, and was conducted on 72 patients between March 2014 and March 2024 at Taleghani Pediatric Hospital in Gorgan, Iran. RESULT: The average age was 18.8 ± 30.3 months, with the majority being boys (62.5%). Most participants had CCAM (41.7%), followed by CLE (18.1%), BPS (16.7%), pulmonary hypoplasia (9.7%), BC (8.3%), and hybrid lesion (5.6%). The majority of patients were Fars (62.5%), and the average hospitalization days was 9.4 ± 4.5 days. Cardiac anomalies were observed in 19.4% of the patients. 62 patients (86.1%) exhibited respiratory symptoms, and prenatal screening during pregnancy led to the diagnosis in 51 patients (70.8%). Most patients had left lung anomalies (43; 59.7%), and the majority (90.3%) survived. There is a statistically significant relation between needed for surgical treatment and patients' type of pulmonary lesions (p-value: 0.02). In addition, there was a significant relation between the Fars ethnicity and the presence of cardiac anomalies (p-value: 0.04). CONCLUSION: Some CLAs remain undiagnosed or untreated due to the rare nature of congenital lung anomalies. Nevertheless, improvements in ultrasound and other imaging methods will make diagnosing and managing these anomalies during the prenatal period more prevalent, resulting in enhanced understanding.

Recurrent spontaneous pneumothorax secondary to lung cystic lesions in a case of convalescent COVID-19: a case report and literature review.

BACKGROUND: While spontaneous pneumothorax has been documented in COVID-19 patients, reports on recurrent spontaneous pneumothorax due to cystic lesions in convalescent COVID-19 patients are scarce. The progression of these lung cystic lesions remains inadequately explored. CASE PRESENTATION AND LITERATURE REVIEW: An 81-year-old male, a non-smoker with a history of rheumatoid arthritis, presented with fever, cough, and expectoration for 14 days. Initially diagnosed with moderate COVID-19, he deteriorated to severe COVID-19 despite adherence to local treatment guidelines. Successive identification of three cystic lesions termed "bulla" or "pneumatocele", and one cystic lesion with air-fluid level, referred to as "pneumo-hamatocele" (PHC), occurred in his lungs. Gradual improvement followed anti-inflammatory therapy and optimal supportive care. However, on day 42, sudden worsening dyspnea prompted a computed tomography (CT) scan, confirming a right spontaneous pneumothorax and subcutaneous emphysema, likely due to PHC rupture. Discharge followed chest tube implementation for pneumothorax resolution. On day 116, he returned to the hospital with mild exertional dyspnea. Chest CT revealed recurrent right pneumothorax from a remaining cyst in the right lung. Apart from our patient, literature retrieval identified 22 COVID-19 patients with spontaneous pneumothorax due to cystic lesions, with a male predominance (95.6%; 22/23). Diagnosis of pneumothorax and lung cystic lesions occurred around day 29.5 (range: 18-35) and day 26.4 (± 9.8) since symptom onset, respectively. Except for one patient whose pneumothorax occurred on day seven of illness, all patients eventually recovered. CONCLUSIONS: Recurrent spontaneous pneumothorax secondary to lung cystic lesions may manifest in convalescent COVID-19 patients, particularly males with COVID-19 pneumonia. Chest CT around 2 to 3 weeks post-symptom onset may be prudent to detect cystic lesion development and anticipate spontaneous pneumothorax.

Regulation of macrophage activation by lactylation in lung disease.

Lactylation is a process where lactate, a cellular metabolism byproduct, is added to proteins, altering their functions. In the realm of macrophage activation, lactylation impacts inflammatory response and immune regulation. Understanding the effects of lactylation on macrophage activation is vital in lung diseases, as abnormal activation and function are pivotal in conditions like pneumonia, pulmonary fibrosis, COPD, and lung cancer. This review explores the concept of lactylation, its regulation of macrophage activation, and recent research progress in lung diseases. It offers new insights into lung disease pathogenesis and potential therapeutic targets.

PPCRKB: a risk factor knowledge base of postoperative pulmonary complications.

Postoperative pulmonary complications (PPCs) are highly heterogeneous disorders with diverse risk factors frequently occurring after surgical interventions, resulting in significant financial burdens, prolonged hospitalization and elevated mortality rates. Despite the existence of multiple studies on PPCs, a comprehensive knowledge base that can effectively integrate and visualize the diverse risk factors associated with PPCs is currently lacking. This study aims to develop an online knowledge platform on risk factors for PPCs (Postoperative Pulmonary Complications Risk Factor Knowledge Base, PPCRKB) that categorizes and presents the risk and protective factors associated with PPCs, as well as to facilitate the development of individualized prevention and management strategies for PPCs based on the needs of each investigator. The PPCRKB is a novel knowledge base that encompasses all investigated potential risk factors linked to PPCs, offering users a web-based platform to access these risk factors. The PPCRKB contains 2673 entries, 915 risk factors that have been categorized into 11 distinct groups. These categories include habit and behavior, surgical factors, anesthetic factors, auxiliary examination, environmental factors, clinical status, medicines and treatment, demographic characteristics, psychosocial factors, genetic factors and miscellaneous factors. The PPCRKB holds significant value for PPC research. The inclusion of both quantitative and qualitative data in the PPCRKB enhances the ability to uncover new insights and solutions related to PPCs. It could provide clinicians with a more comprehensive perspective on research related to PPCs in future. Database URL: http://sysbio.org.cn/PPCs.

Single-cell transcriptomics by clinical course of Mycobacterium avium complex pulmonary disease.

Mycobacterium avium complex pulmonary disease (MAC-PD) has a heterogeneous clinical course. However, immune profiles associated with MAC-PD clinical course are limited. We performed single-cell RNA sequencing of peripheral blood mononuclear cells from 21 MAC-PD patients divided into three clinical courses: group A, spontaneous culture conversion; group B, stable disease without antibiotic treatment; and group C, progressive disease with antibiotic treatment. A lower proportion of NK cells and higher proportion of monocytes were noted in group C compared to combined groups A and B. The proportion of classical monocytes was higher in group C compared to groups A and B, while the proportion of non-classical monocytes decreased. EGR1, HSPA1A, HSPA1B, and CD83 were up-regulated in spontaneous culture conversion group A compared to progressive disease group C. Up-regulation of MYOM2 and LILRA4 and down-regulation of MT-ATP8, CD83, and CCL3L1 was found in progressive disease group C. PCBP1, FOS, RGCC, S100B, G0S2, AREG, and LYN were highly expressed in favorable treatment response compared to unfavorable response. Our findings may offer a comprehensive understanding of the host immune profiles that influence a particular MAC-PD clinical course and could suggest an immunological mechanism associated with the disease progression of MAC-PD.