Chronic Lung Disease Research Articles

PULMONARY REHABILITATION IN ROMANIA: FROM THE BEGINNINGS TO THE PRESENT

Pulmonary rehabilitation is the standard of care for patients with chronic lung disease. Material and method: Starting from the systematic review of specialized literature and practical expertise obtained both internationally and nationally, the exposition emphasizes the aspects related to pulmonary rehabilitation in patients with chronic lung diseases. Results: The cornerstone of pulmonary rehabilitation is the American Thoracic Society (ATS)/European Respiratory Society (ERS) Statement on Pulmonary Rehabilitation published in 2006 and developed based on the documents of the American College of Chest Physicians (ACCP) and American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) published in 1997 and 2004. The document was subsequently updated in 2007, 2013, 2015, 2021 and 2023, with the concept of pulmonary rehabilitation constantly evolving over the years. In Romania, pulmonary rehabilitation is carried out according to these guidelines and international standards, Iasi being a reference center in this field. Conclusions: Pulmonary rehabilitation is one of the most powerful evidence-based therapies for patients with chronic lung disease. Keywords: COPD, exercise capacity, training, quality of life.

Adipose-derived Stem Cells Therapy for Moderate Chronic Obstructive Pulmonary Disease in Adult Subjects: A Phase III Randomized, Multicenter Trial: RESPIRE Protocol

Introduction: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide and has a prevalence of 11.7%. Current treatment focuses on reducing symptoms and exacerbations, as no definitive intervention exists. Regenerative treatments such as mesenchymal stem cell (MSCs) therapy have shown promise in preclinical and clinical studies. This article presents a study protocol to evaluate the efficacy of adipose-derived (AD) MSCs therapy in improving FEV-1 in COPD patients. Methods: A phase III, multicenter, randomized, double-blind, placebo-controlled study is proposed to test the clinical safety and efficacy of AD-MSC therapy in patients with COPD. The population is subjects with COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 (50%≤FEV1<80% predicted) and Group D (two exacerbations or one hospitalization and mMRC>2 or CAT>10). This study aims to evaluate the improvement of FEV1 from baseline to 90 days after AD-MSC infusion. The primary outcome is FEV1-improvement (%) over the baseline for the treatment and placebo groups, assessed on study day 90 vs. baseline (day 0). For the primary outcome, the statistical analysis will use the Mann-Whitney U test to analyze the FEV1 for the treatment and control groups at 90 days against the baseline. Discussion: Aside from symptomatic relief, there is a growing demand for a curative treatment for COPD. The potential of novel AD-MSCs therapies for COPD improvement is currently in early development. Preclinical, phase I, and a few phase II studies for AD-MSCs as a COPD treatment have proven optimistic results. This phase III, randomized, multicenter trial proposes evaluating an alternative treatment for this condition that may improve lung function.

Pulmonary Hypertension Associated with Chronic Lung Disease

Abstract: Patients with Chronic Lung Disease (CLD) are frequently burdened by pulmonary hypertension (PH), which is associated with reduced functional capacity, poor quality of life, increased oxygen requirements, and increased morbidity and mortality. The development of PH associated with chronic lung disease (PH-CLD) is complex and multifactorial and varies between different types of CLD. In this review, we provide an update on PH-CLD, with a particular focus on Interstitial Lung Disease (ILD), chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), and obesity hypoventilation syndrome (OHS). We discussed epidemiology, histopathology, pathophysiology, diagnostic evaluation, and treatment approaches. There are limited data on the use of pulmonary arterial hypertension-specific treatments in PH-CLD, so it has been proposed to phenotype patients based on their degree of pulmonary vascular disease to guide individualized care. The heterogeneity within PH-CLD highlights the importance of identifying novel molecular pathways unique to each subgroup to ultimately achieve precision medicine.

Interchanging Reusable and Disposable Nebulizers Used with Home-Based Compressors May Result in Inconsistent Dosing: A Laboratory Investigation with Device Combinations Supplied to the US Healthcare Environment.

Reusable nebulizer-compressor combinations deliver inhaled medications for patients with chronic lung diseases. On hospital discharge, the patient may take home the disposable nebulizer that was packagedand combine it with their home compressor. Though this practice may reduce waste, it can increase variability in medication delivery. Our study compared several reusable and disposable nebulizers packaged with compressor kits used in the US. We included a common disposable hospital nebulizer that may not be supplied with popular home kits but may be brought home after a hospitalization or emergency department visit. We focused on fine droplet mass < 4.7 μm aerodynamic diameter (FDM<4.7 μm), associated with medication delivery to the airways of the lungs. We evaluated the following nebulizer-compressor combinations (n = 5 replicates): 1. OMBRA® Table Top Compressor with MC 300® reusable and Airlife™ MistyMax™ 10® disposable nebulizer, 2. Sami-the-Seal® compressor with SideStream® reusable and disposable nebulizers and Airlife™ MistyMax 10™ disposable nebulizer, 3. VIOS® compressor with LC Sprint® reusable, and VixOne® and Airlife™ MistyMax™ disposable nebulizers, 4. Innospire® Elegance® compressor with SideStream® reusable and disposable nebulizers and Airlife™ MistyMax 10™ disposable nebulizer, 5. Willis-the-Whale® compressor with SideStream® reusable and disposable nebulizers and Airlife™ MistyMax 10™ disposable nebulizer, 6. Pari PRONEB® Max compressor with LC Sprint® reusable and Airlife™ MistyMax 10™ disposable nebulizer. We placed a 3-ml albuterol solution (0.833 mg/ml) in each nebulizer. A bacterial/viral filter was attached to the nebulizer mouthpiece to capture emitted medication, with the filter exit coupled to a simulator of a tidal breathing adult (rate = 10 cycles/min; Vt = 600 ml; I/E ratio = 1:2). The filter was replaced at 1-min intervals until onset of sputter. Droplet size distributions (n = 5 replicates/system) were determined in parallel by laser diffractometry. Cumulative FDM<4.7 μm varied from 381 ± 33 μg for the best performing combination (Proneb/LC-Sprint) to 150 ± 21 μg for the system with the lowest output (VIOS®/MistyMax 10™). Substituting one nebulizer for another can result in large differences in medication delivery to the lungs.

Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus

Coronavirus disease 2019 (COVID-19) is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus. It has affected over 768 million people worldwide, resulting in approximately 6900000 deaths. High-risk groups, identified by the Centers for Disease Control and Prevention, include individuals with conditions like type 2 diabetes mellitus (T2DM), obesity, chronic lung disease, serious heart conditions, and chronic kidney disease. Research indicates that those with T2DM face a heightened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals. Examining the renin-angiotensin system (RAS), a vital regulator of blood pressure and pulmonary stability, reveals the significance of the angiotensin-converting enzyme (ACE) and ACE2 enzymes. ACE converts angiotensin-I to the vasoconstrictor angiotensin-II, while ACE2 counters this by converting angiotensin-II to angiotensin 1-7, a vasodilator. Reduced ACE2 expression, common in diabetes, intensifies RAS activity, contributing to conditions like inflammation and fibrosis. Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels, concerns arise regarding the potential elevation of ACE2 receptors on cell membranes, potentially facilitating COVID-19 entry. This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome coronavirus 2 infection and associated complications in T2DM. Potential treatment strategies, including recombinant human ACE2 therapy, broad-spectrum antiviral drugs, and epigenetic signature detection, are discussed as promising avenues in the battle against this pandemic.

Household Air Pollution Interventions to Improve Health in Low- and Middle-Income Countries: An Official American Thoracic Society Research Statement.

Background: An estimated 3 billion people, largely in low- and middle-income countries, rely on unclean fuels for cooking, heating, and lighting to meet household energy needs. The resulting exposure to household air pollution (HAP) is a leading cause of pneumonia, chronic lung disease, and other adverse health effects. In the last decade, randomized controlled trials of clean cooking interventions to reduce HAP have been conducted. We aim to provide guidance on how to interpret the findings of these trials and how they should inform policy makers and practitioners.Methods: We assembled a multidisciplinary working group of international researchers, public health practitioners, and policymakers with expertise in household air pollution from within academia, the American Thoracic Society, funders, nongovernmental organizations, and global organizations, including the World Bank and the World Health Organization. We performed a literature search, convened four sessions via web conference, and developed consensus conclusions and recommendations via the Delphi method.Results: The committee reached consensus on 14 conclusions and recommendations. Although some trials using cleaner-burning biomass stoves or cleaner-cooking fuels have reduced HAP exposure, the committee was divided (with 55% saying no and 45% saying yes) on whether the studied interventions improved measured health outcomes.Conclusions: HAP is associated with adverse health effects in observational studies. However, it remains unclear which household energy interventions reduce exposure, improve health, can be scaled, and are sustainable. Researchers should engage with policy makers and practitioners working to scale cleaner energy solutions to understand and address their information needs.

Sudden death due to spontaneous rupture of the right atrium in the setting of chronic lung disease: A case report and review.

Sudden death from haemopericardium as a result of a right atrial rupture is uncommon, most particularly when this occurs spontaneously without any prior trauma or evidence of atrial wall pathology. The deceased was a 32-year-old man. At lunchtime his symptoms of unease, giddiness and unconsciousness began and within 45 minutes he arrived at the hospital. His vitals could not be recorded in the emergency department, and after CPR, he was pronounced dead. At autopsy, an isolated right atrial rupture, without any disease of the heart wall, was discovered. The right atrium has the weakest wall and is frequently the site of spontaneous rupture brought on by increased intraluminal pressure. Both liquid blood and clotted blood were found in the pericardial cavity. Low atrial pressure encourages clot formation because it causes considerably slower blood entry into the pericardium at the time of atrial rupture compared with entry at the time of ventricular rupture. Evidence of chronic lung disease was found which explains the raised intraluminal pressure of the heart chambers. Even with no history of trauma or myocardial infarction, the Beck triad - an engorged neck vein, a muffled heart sound, and low blood pressure - should alert the emergency room staff to the possibility of cardiac tamponade because, in a very unlikely scenario, spontaneous cardial wall rupture might occur.

Reactivation of Varicella-Zoster Virus in Patients with Lung Cancer Receiving Immune Checkpoint Inhibitors: Retrospective Nationwide Population-Based Cohort Study from South Korea

Background: This study aimed to determine the association between immune checkpoint inhibitors (ICIs) and the risk of herpes zoster (HZ) incidence in patients with lung cancer. Method: We obtained national claims data of 51,021 patients from South Korea with lung cancer between August 2017 and December 2021. The study population was classified into ICI and non-ICI groups based on the prescription of ICIs at least once during the study period. To estimate the effects of ICIs treatment compared with those without ICIs treatment on HZ incidence, we used the Cox proportional hazards model adjusted for sex, age, comorbidities, and concomitant use of immunosuppressive drugs. Stratified analyses based on sex, age, and comorbidities were conducted to identify corresponding risk factors. Results: Of the 51,021 study participants, 897 (1.8%) were prescribed ICIs and 2262 (4.4%) were diagnosed with HZ. Approximately 75.6% of the patients receiving ICIs were male, and the prevalence of diabetes, cardiovascular disease, and chronic lung disease in the ICI group was significantly lower than that in the non-ICIs group. The Kaplan–Meier plot showed that the probability of incidence of HZ in the ICIs group was lower than that in the non-ICIs group. Additionally, treatment with ICIs was associated with a 31% lower incidence of developing HZ when compared to that seen without ICIs treatment (95% confidence interval [CI], 0.48–1.00). This association was stronger in females (hazard ratio [HR], 0.42; 95% CI, 0.19–0.94) and those less than 68 years of age (HR, 0.58; 95% CI, 0.34–0.99). Conclusions: In these real-world data from an Asian population with lung cancer, ICIs treatment might be associated with a reduced risk of HZ compared to that without ICIs treatment.

Metabolomic Analysis Reveals the Association of Severe Bronchopulmonary Dysplasia with Gut Microbiota and Oxidative Response in Extremely Preterm Infants

Bronchopulmonary dysplasia (BPD) is a chronic lung disease mainly affecting premature infants needing ventilation or oxygen for respiratory distress. This study aimed to evaluate the molecular linkages for BPD in very and extremely preterm infants using a metabolomics-based approach. A case-control study of enrolling preterm infants born before 32 weeks gestational age (GA) was prospectively performed. These preterm infants were subsequently stratified into the following two groups for further analysis: no or mild BPD, and moderate or severe BPD based on the 2019 NICHD criteria. Urinary metabolomic profiling was performed using 1H-Nuclear magnetic resonance (NMR) spectroscopy coupled with partial least squares discriminant analysis (PLS-DA) at a corrected age of 6 months. Metabolites significantly differentially related to GA and BPD severity were performed between groups, and their roles in functional metabolic pathways were also assessed. A total of 89 preterm infants born before 32 weeks gestation and 50 infants born at term age (above 37 completed weeks’ gestation) served as controls and were enrolled into the study. There were 21 and 24 urinary metabolites identified to be significantly associated with GA and BPD severity, respectively (p &lt; 0.05). Among them, N-phenylacetylglycine, hippurate, acetylsalicylate, gluconate, and indoxyl sulfate were five metabolites that were significantly higher, with the highest importance in both infants with GA &lt; 28 weeks and those with moderate to severe BPD, whereas betaine and N,N-dimethylglycine were significantly lower (p &lt; 0.05). Furthermore, ribose and a gluconate related pentose phosphate pathway were strongly associated with these infants (p &lt; 0.01). In conclusion, urinary metabolomic analysis highlights the crucial role of gut microbiota dysbiosis in the pathogenesis of BPD in preterm infants, accompanied by metabolites related to diminished antioxidative capacity, prompting an aggressive antioxidation response in extremely preterm infants with severe BPD.

Codonopsis Radix inhibits the inflammatory response and oxidative stress in Chronic Obstructive Pulmonary Disease mice through regulation of the Nrf2/NF-κB signaling pathway.

Chronic Obstructive Pulmonary Disease (COPD) is a non-specific chronic inflammatory lung disease with no known cure. Codonopsis Radix(CR) has been shown to exhibit anti-inflammatory and antioxidant effects. Therefore, this study aimed to investigate the potential anti-inflammatory effects of different CR variety on COPD mice. 60 male specified pathogen free (SPF)-grade C57BL/6J mice were randomly divided into 6 groups, 10 mice in each group. The COPD mice model was induced by cigarette smoke extract (CSE) combined with lipopolysaccharide (LPS), and the mice in each group were given corresponding drugs. Lung function was assessed in all mice. Lung tissues were stained with hematoxylin-eosin (HE), Masson, and periodic acid shiff (PAS) stains, and serum levels of interleukin (IL)-8 and tumor necrosis factor (TNF)-α were detected using an enzyme-linked immunosorbent assay (ELISA). Further, serum and lung tissue levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by colorimetric assay. Network pharmacology and molecular docking was used to predict signalling pathways, which were validated by western blot analysis. Compared with the COPD group, the mice in each dosing group of CR exhibited significant reductions in serum IL-8 and TNF-α levels, serum and lung tissue MDA levels, and pathological lung tissue damage, alongside elevations in lung function and SOD levels (P<0.01). Western blot analysis also indicated significant down-regulation of p-p65/p65 and p-IκB-α/IκB-α protein expression, alongside significant up-regulation of Nrf2 protein expression in the lung tissues of mice treated with CR (P<0.01). In summary, CR effectively enhances lung function, minimizes lung tissue damage, and inhibits inflammation and oxidative stress in mice with COPD. Additionally, these findings suggest that inhibition of the Nrf2/NF-κB axis may be a key mechanism of action of CR in the alleviation of COPD.

Application of the ERS/ATS Spirometry Standards and Race-Neutral Equations in the COPDGene Study.

The European Respiratory Society (ERS) and the American Thoracic Society (ATS) recommend using z-scores, and the ATS has recommended using Global Lung Initiative (GLI)- "Global" race-neutral reference equations for spirometry interpretation. However, these recommendations have been variably implemented and the impact has not been widely assessed, both in clinical and research settings. We evaluated the ERS/ATS airflow obstruction severity classification. In the COPDGene Study (n = 10,108), airflow obstruction has been defined as a forced expiratory volume in one second to forced vital capacity (FEV1/FVC) ratio <0.70, with spirometry severity graded from class 1 to 4 based on race-specific percent predicted (pp) FEV1 cut-points as recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We compared the GOLD approach, using NHANES III race-specific equations, to the application of GLI-Global equations using the ERS/ATS definition of airflow obstruction as FEV1/FVC ratio < lower limit of normal (LLN) and z-FEV1 cut-points of -1.645, -2.5, and -4 ("zGLI Global"). We tested the four-tier severity scheme for association with COPD outcomes. The lowest agreement between ERS/ATS with zGLI Global and the GOLD classification was observed in individuals with milder disease (56.9% and 42.5% in GOLD 1 and 2) and race was a major determinant of redistribution. After adjustment for relevant covariates, zGLI Global distinguished all-cause mortality risk between normal spirometry and the first grade of COPD (Hazard Ratio 1.23, 95% CI 1.04-1.44, p=0.014), and showed a linear increase in exacerbation rates with increasing disease severity, in comparison to GOLD. The zGLI Global severity classification outperformed GOLD in the discrimination of survival, exacerbations, and imaging characteristics.

[64Cu]Cu-PEG-FUD peptide for noninvasive and sensitive detection of murine pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease resulting in irreversible scarring within the lungs. However, the lack of biomarkers that enable real-time assessment of disease activity remains a challenge in providing efficient clinical decision-making and optimal patient care in IPF. Fibronectin (FN) is highly expressed in fibroblastic foci of the IPF lung where active extracellular matrix (ECM) deposition occurs. Functional upstream domain (FUD) tightly binds the N-terminal 70-kilodalton domain of FN that is crucial for FN assembly. In this study, we first demonstrate the capacity of PEGylated FUD (PEG-FUD) to target FN deposition in human IPF tissue ex vivo. We subsequently radiolabeled PEG-FUD with 64Cu and monitored its spatiotemporal biodistribution via μPET/CT imaging in mice using the bleomycin-induced model of pulmonary injury and fibrosis. We demonstrated [64Cu]Cu-PEG-FUD uptake 3 and 11 days following bleomycin treatment, suggesting that radiolabeled PEG-FUD holds promise as an imaging probe in aiding the assessment of fibrotic lung disease activity.

Cohort profile: the PERSIAN Dena Cohort Study (PDCS) of non-communicable diseases in Southwest Iran

PurposeThis study conducted in Dena County is a population-based cohort study as part of the Prospective Epidemiological Research Studies in Iran (PERSIAN). The specific objectives of this study were to...

Exosomes: efficient macrophage-related immunomodulators in chronic lung diseases

Macrophages, the predominant immune cells in the lungs, play a pivotal role in maintaining the delicate balance of the pulmonary immune microenvironment. However, in chronic inflammatory lung diseases and lung cancer, macrophage phenotypes undergo distinct transitions, with M1-predominant macrophages promoting inflammatory damage and M2-predominant macrophages fostering cancer progression. Exosomes, as critical mediators of intercellular signaling and substance exchange, participate in pathological reshaping of macrophages during development of pulmonary inflammatory diseases and lung cancer. Specifically, in inflammatory lung diseases, exosomes promote the pro-inflammatory phenotype of macrophages, suppress the anti-inflammatory phenotype, and subsequently, exosomes released by reshaped macrophages further exacerbate inflammatory damage. In cancer, exosomes promote pro-tumor tumor-associated macrophages (TAMs); inhibit anti-tumor TAMs; and exosomes released by TAMs further enhance tumor proliferation, metastasis, and resistance to chemotherapy. Simultaneously, exosomes exhibit a dual role, holding the potential to transmit immune-modulating molecules and load therapeutic agents and offering prospects for restoring immune dysregulation in macrophages during chronic inflammatory lung diseases and lung cancer. In chronic inflammatory lung diseases, this is manifested by exosomes reshaping anti-inflammatory macrophages, inhibiting pro-inflammatory macrophages, and alleviating inflammatory damage post-reshaping. In lung cancer, exosomes reshape anti-tumor macrophages, inhibit pro-tumor macrophages, and reshaped macrophages secrete exosomes that suppress lung cancer development. Looking ahead, efficient and targeted exosome-based therapies may emerge as a promising direction for treatment of pulmonary diseases.

Inhaled bronchodilators for the prevention and treatment of chronic lung disease in preterm infants.

Chronic lung disease (CLD) occurs frequently in preterm infants and is associated with respiratory morbidity. Bronchodilators have the potential effect of dilating small airways with muscle hypertrophy. Increased compliance and tidal volume, and decreased airway resistance, have been documented with the use of bronchodilators in infants with CLD. Therefore, bronchodilators are widely considered to have a role in the prevention and treatment of CLD, but there remains uncertainty as to whether they improve clinical outcomes. This is an update of the 2016 Cochrane review. To determine the effect of inhaled bronchodilators given as prophylaxis or as treatment for chronic lung disease (CLD) on mortality and other complications of preterm birth in infants at risk for or identified as having CLD. An Information Specialist searched CENTRAL, MEDLINE, Embase, CINAHL and three trials registers from 2016 to May 2023. In addition, the review authors undertook reference checking, citation searching and contact with trial authors to identify additional studies. We included randomised and quasi-randomised controlled trials involving preterm infants less than 32 weeks old that compared bronchodilators to no intervention or placebo. CLD was defined as oxygen dependency at 28 days of life or at 36 weeks' postmenstrual age. Initiation of bronchodilator therapy for the prevention of CLD had to occur within two weeks of birth. Treatment of infants with CLD had to be initiated before discharge from the neonatal unit. The intervention had to include administration of a bronchodilator by nebulisation or metered dose inhaler. The comparator was no intervention or placebo. We used the standard methodological procedures expected by Cochrane. Critical outcomes included: mortality within the trial period; CLD (defined as oxygen dependency at 28 days of life or at 36 weeks' postmenstrual age); adverse effects of bronchodilators, including hypokalaemia (low potassium levels in the blood), tachycardia, cardiac arrhythmia, tremor, hypertension and hyperglycaemia (high blood sugar); and pneumothorax. We used the GRADE approach to assess the certainty of the evidence for each outcome. We included two randomised controlled trials in this review update. Only one trial provided useable outcome data. This trial was conducted in six neonatal intensive care units in France and Portugal, and involved 173 participants with a gestational age of less than 31 weeks. The infants in the intervention group received salbutamol for the prevention of CLD. The evidence suggests that salbutamol may result in little to no difference in mortality (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.50 to 2.31; risk difference (RD) 0.01, 95% CI -0.09 to 0.11; low-certainty evidence) or CLD at 28 days (RR 1.03, 95% CI 0.78 to 1.37; RD 0.02, 95% CI -0.13 to 0.17; low-certainty evidence), when compared to placebo. The evidence is very uncertain about the effect of salbutamol on pneumothorax. The one trial with usable data reported that there were no relevant differences between groups, without providing the number of events (very low-certainty evidence). Investigators in this study did not report if side effects occurred. We found no eligible trials that evaluated the use of bronchodilator therapy for the treatment of infants with CLD. We identified no ongoing studies. Low-certainty evidence from one trial showed that inhaled bronchodilator prophylaxis may result in little or no difference in the incidence of mortality or CLD in preterm infants, when compared to placebo. The evidence is very uncertain about the effect of salbutamol on pneumothorax, and neither included study reported on the incidence of serious adverse effects. We identified no trials that studied the use of bronchodilator therapy for the treatment of CLD. Additional clinical trials are necessary to assess the role of bronchodilator agents in the prophylaxis or treatment of CLD. Researchers studying the effects of inhaled bronchodilators in preterm infants should include relevant clinical outcomes in addition to pulmonary mechanical outcomes.

Pulmonary Rehabilitation: A Look Back, a Look Forward.

Pulmonary rehabilitation (PR) is a comprehensive approach to the management of patients with chronic lung disease that encompasses exercise, education, and psychosocial support. The development of PR programs began in the mid-20th century with the appreciation that exercise provided real benefit in chronic lung disease and that effective disease management involved patient education focused on medications, lifestyle changes, and lifelong regular exercise. Initially PR was primarily facility-based, but today PR is extending into the home with telemedicine, and this is encouraging a real partnership of patients and professionals supporting self-management. The evidence base supporting PR as a safe and effective modality has grown exponentially over the last 4 decades, and PR is strongly endorsed by virtually all the major professional societies. Importantly, PR has also clearly been shown to be cost-effective. Challenges remain, however. Access is still very limited for a variety of reason (logistics, financial, patient motivation) that need to be addressed. More focused and personalized exercise programs and monitoring strategies that encourage a patient's lifetime commitment to the principles of PR need to be developed and refined. The opportunity to really impact important clinical outcomes exists with PR, and this needs to be exploited.

Clinical phenotyping in patients with anti-synthetase antibodies using cluster analysis

Abstract Objectives To characterize clinically distinct subgroups among unselected patients with anti-synthetase antibodies using cluster analysis. Methods This study evaluated patients with anti-synthetase antibodies registered to two independent cohorts; 106 consecutive patients from a prospective, single-centre cohort of the Scleroderma/Myositis Centre of Excellence (SMCE) were used as a derivation cohort, while 125 patients from the Multicentre Retrospective Cohort of Japanese Patients with Myositis-Associated Interstitial lung disease (JAMI) were used as a validation cohort. Anti-synthetase antibodies were identified by RNA immunoprecipitation. A multiple correspondence analysis followed by hierarchical clustering was performed to aggregate the patients into homogenous subgroups. Subsequently, a simple-to-use classification tree was generated using classification and regression tree analysis. Results Three clusters were identified in the SMCE cohort: cluster #1 (n = 48), the “interstitial pneumonia with autoimmune features/amyopathic dermatomyositis cluster” associated with older age at diagnosis and a higher frequency of malignancy; cluster #2 (n = 46), the “dermatomyositis (DM) cluster”, corresponded to a younger age at diagnosis with a higher prevalence of myositis, arthritis, DM-pathognomonic rashes, mechanic's hands, and fever; and cluster #3 (n = 12), the “systemic sclerosis cluster”, characterized by chronic interstitial lung disease. There was no significant difference in overall survival or progression-free survival between the clusters. A simple classification tree using myositis and Raynaud’s phenomenon was created in the SMCE cohort. Clusters #1 and #2 were successfully reproduced and the classification tree demonstrated favourable performance in the JAMI cohort. Conclusion Patients with anti-synthetase antibodies were classified into three distinct phenotypes, indicating substantial heterogeneity within this patient group.

Revolutionizing the Treatment of Idiopathic Pulmonary Fibrosis: From Conventional Therapies to Advanced Drug Delivery Systems.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease that has been well-reported in the medical literature. Its incidence has risen, particularly in light of the recent COVID-19 pandemic. Conventionally, IPF is treated with antifibrotic drugs-pirfenidone and nintedanib-along with other drugs for symptomatic treatments, including corticosteroids, immunosuppressants, and bronchodilators based on individual requirements. Several drugs and biologicals such as fluorofenidone, thymoquinone, amikacin, paclitaxel nifuroxazide, STAT3, and siRNA have recently been evaluated for IPF treatment that reduces collagen formation and cell proliferation in the lung. There has been a great deal of research into various treatment options for pulmonary fibrosis using advanced delivery systems such as liposomal-based nanocarriers, chitosan nanoparticles, PLGA nanoparticles, solid lipid nanocarriers, and other nanoformulations such as metal nanoparticles, nanocrystals, cubosomes, magnetic nanospheres, and polymeric micelles. Several clinical trials are also ongoing for advanced IPF treatments. This article elaborates on the pathophysiology of IPF, its risk factors, and different advanced drug delivery systems for treating IPF. Although extensive preclinical data is available for these delivery systems, the clinical performance and scale-up studies would decide their commercial translation.

Inhalable FN-binding liposomes or liposome-exosome hybrid bionic vesicles encapsulated microparticles for enhanced pulmonary fibrosis therapy

Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease that seriously threatens human life and health. Our previous study demonstrated the unique superiority of traditional Chinese medicine cryptotanshinone (CTS) combined with sustained pulmonary drug delivery for treating PF. In this study, we aimed to enhance the selectivity, targeting efficiency and sustained-release capability based on this delivery system. To this end, we developed and evaluated CTS-loaded modified liposomes-chitosan (CS) microspheres SM(CT-lipo) and liposome-exosome hybrid bionic vesicles-CS microspheres SM(LE). The prepared nano-in-micro particles system integrates the advantages of the carriers and complements each other. SM(CT-lipo) and SM(LE) achieved lung myofibroblast-specific targeting through CREKA peptide binding specifically to fibronectin (FN) and the homing effect of exosomes on parent cells, respectively, facilitating efficient delivery of anti-fibrosis drugs to lung lesions. Furthermore, compared with daily administration of conventional microspheres SM(NC) and positive control drug pirfenidone (PFD), inhaled administration of SM(CT-lipo) and SM(LE) every two days still attained similar efficacy, exhibiting excellent sustained drug release ability. In summary, our findings suggest that the developed SM(CT-lipo) and SM(LE) delivery strategies could achieve more accurate, efficient and safe therapy, providing novel insights into the treatment of chronic PF.

Assessing the agreement of chronic lung disease of prematurity diagnosis between radiologists and clinical criteria

BackgroundChronic lung disease of prematurity (CLD) is the most prevalent complication of preterm birth and indicates an increased likelihood of long-term pulmonary complications. The accurate diagnosis of this condition is critical for long-term health management. Numerous definitions define CLD with different clinical parameters and radiology findings, making diagnosis of the disease ambiguous and potentially inaccurate.Methods95 patients were identified for this study, as determined by the diagnosis or confirmation of CLD in the impression of the radiologist’s report on chest x-ray. Pulmonary function and complications were recorded at multiple benchmark timeframes within each patient’s first few months of life and used for determining eligibility under each definition.ResultsEach clinical definition of CLD had a high sensitivity for patients identified to have CLD by radiologists, correctly fitting over 90% of patients. Most patients included required invasive mechanical ventilation or positive pressure ventilation at 36 weeks postmenstrual age, indicating patients with radiographically confirmed CLD tended to have more severe disease. Radiologists tended to diagnose CLD before 36 weeks postmenstrual age, a timepoint used by multiple standard clinical definitions, with cases called earlier fitting under a larger percentage of definitions than those called later.ConclusionsRadiologists tend to diagnose CLD in young patients with severe respiratory compromise, and can accurately diagnose the condition before developmental milestones for clinical definitions are met.