Lung Disease Research Articles

Infection and Inflammation in the Cystic fibrosis (CF) airway.

Cystic fibrosis (CF) airway disease is characterized by chronic infection and neutrophil-driven inflammation, leading to progressive airway damage and early mortality. Infection with Pseudomonas aeruginosa significantly impacts morbidity and mortality, requiring early detection and aggressive antibiotic treatment. Controlling inflammation remains difficult due to the limited availability of effective anti-inflammatory treatments. CFTR modulators show potential in reducing inflammation, but further research is needed. Effective management of CF lung disease requires a comprehensive approach addressing both infection and inflammation.

Different phenotypes with different endings-Telomere biology disorders and cancer predisposition with long telomeres.

Rare germline pathogenic variants (GPVs) in genes essential in telomere length maintenance and function have been implicated in two broad classes of human disease. The telomere biology disorders (TBDs) are a spectrum of life-threatening conditions, including bone marrow failure, liver and lung disease, cancer and other complications caused by GPVs in telomere maintenance genes that result in short and/or dysfunctional telomeres and reduced cellular replicative capacity. In contrast, cancer predisposition with long telomeres (CPLT) is a disorder associated with elevated risk of a variety of cancers, primarily melanoma, thyroid cancer, sarcoma, glioma and lymphoproliferative neoplasms caused by GPVs in shelterin complex genes that lead to excessive telomere elongation and increased cellular replicative capacity. While telomeres are at the root of both disorders, the term TBD is used to convey the clinical phenotypes driven by critically short or otherwise dysfunctional telomeres and their biological consequences.

Analysis of Lung Disease Prediction using Machine Learning Algorithms

Lung diseases are a notable in global health concern, requiring early diagnosis for better recovery and survival rates. Deep learning strategies, especially CNNs, have shown great promise in self learning lung disease diagnosis from medical images like chest X-rays. Ensemble learning methods using pretrained networks such as VGG16, InceptionV3, and MobileNetV2 have achieved up to 94% accuracy in identifying conditions like COVID-19, pneumonia, and lung opacity. Lightweight CNN models also performed well, with accuracy up to 89.89%. Traditional machine learning algorithms, including Random Forest and Logistic Regression, yielded accuracy rates between 88% and 90%. A hybrid deep learning approach, combining CNN based feature extraction with classifiers like AdaBoost, SVM, and Random Forest, improved classification accuracy by 3.1% and reduced computational complexity by 16.91%. This hybrid method highlights the main feature for integrating deep learning with traditional classifiers to enhance lung disease detection efficiency

The gut microbiota modulates airway inflammation in allergic asthma through the gut-lung axis related immune modulation: A review.

The human gut microbiota is a vast and complex microbial community. According to statistics, the number of bacteria residing in the human intestinal tract is approximately 10 times that of total human cells, with over 1,000 different species. The interaction between the gut microbiota and various organ tissues plays a crucial role in the pathogenesis of local and systemic diseases, exerting a significant influence on disease progression. The relationship between the gut microbiota and intestinal diseases, along with its connection to the pulmonary immune environment and the development of lung diseases, is commonly referred to as the "gut-lung axis." The incidence of bronchial asthma is rising globally. With ongoing research on gut microbiota, it is widely believed that intestinal microorganisms and their metabolic products directly or indirectly participate in the occurrence and development of asthma. Based on the gut-lung axis, this review examines recent research suggesting that the intestinal microbiota can influence the occurrence and progression of allergic asthma through the modulation of cytokine immune balance and mucosal integrity. Though the precise immune pathways or microbial species influencing asthma through the gut-lung axis are still under exploration, summarizing the immune modulation through the gut-lung axis in allergic asthma may provide insights for the clinical management of the condition.

Cohort study of serological biomarkers for interstitial lung disease in patients with rheumatoid arthritis

Objective Interstitial lung disease (ILD) is an important cause of mortality in patients with rheumatoid arthritis (RA). Early RA-ILD detection is essential to improve prognosis. Here, we investigated eight serological biomarkers that may contribute to RA-ILD detection. Method Fifty-five patients from the Early Rheumatoid Arthritis Program were evaluated for ILD with high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) using the SCAPIS protocol. Blood samples were obtained for biomarker analysis, and patients’ clinical records were reviewed. We defined ILD using five different models based on the measurements used to confirm ILD: Model A = HRCT; B = PFTs; C = A plus B; D = C plus symptoms; and E = D plus inhalations. Results Among 55 patients, two had an ILD diagnosis before the study, but over one-third fulfilled the ILD criteria. Cancer antigen 15-3 (CA15-3) and matrix metalloproteinase-7 (MMP-7) differentiated between RA with and without ILD (all p < 0.05). Surfactant protein D (SP-D) showed similar trends, as did macrophage inflammatory protein-1β (MIP-1β) and chitinase 3-like protein-1 (YKL-40). Based on Pearson’s correlation coefficients, MIP-1β and YKL-40 were significantly correlated with DAS28 (MIP-1β: 0.3; YKL-40: 0.4), ESR (MIP-1β: 0.3; YKL-40: 0.4), and CRP (only MIP-1β: 0.4) (all p < 0.05). CA15-3 was correlated with rheumatoid factor and anti-citrullinated peptide antibodies (Pearson’s correlation 0.3; both p = 0.03). Conclusions CA15-3 was the most significant biomarker for ILD detection in RA patients with stable low disease activity, closely followed by MMP-7. SP-D, MIP-1β, and YKL-40 may also contribute to RA-ILD diagnosis.

Psychiatric Disorders in Patients with Chronic Obstructive Pulmonary Disease: Clinical Significance and Treatment Strategies

Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease characterized by chronic airflow limitation and persistent respiratory symptoms. It is a major cause of morbidity and mortality worldwide, significantly impacting healthcare systems with considerable socioeconomic consequences. The main risk factors include exposure to tobacco smoke, environmental pollutants, occupational dust, and genetic factors such as alpha-1 antitrypsin deficiency. COPD is often associated with extrapulmonary comorbidities, particularly psychiatric disorders like depression and anxiety, which worsen patients’ quality of life and prognosis. The prevalence of these disorders in patients with COPD varies significantly but is always higher than in healthy controls. Psychiatric disorders can negatively influence COPD management and vice versa, creating a complex bidirectional interaction. Depression and anxiety are the most common psychiatric comorbidities in patients with COPD, influenced by factors such as social isolation, physical limitations, and fear of exacerbations. Diagnosis of these psychiatric disorders is complicated by the overlap of symptoms with those of COPD. However, some screening tools can facilitate early detection. The treatment of psychiatric disorders in patients with COPD in a rehabilitation setting requires a multidisciplinary approach involving pulmonologists, neurologists and psychologists. Pharmacological therapy with antidepressants shows mixed results in terms of efficacy and safety, with some studies reporting benefits on quality of life and others suggesting an increased risk of exacerbations and pneumonia. An integrated approach that includes the assessment and intervention of mental disorders is essential to improve the overall management of COPD and the quality of life of patients. This narrative review provides an overview of the main psychiatric comorbidities in COPD patients, aiming to fill gaps in the literature and suggest areas for future research.

Tobacco Use, Food Insecurity, and Low BMI in India’s Older Population

Background: Underweight is a prevalent condition among older adults in developing countries and poses a substantial burden on health, social, and aged-care systems. In this study, we examined the influence of tobacco use and food insecurity on the risk of being underweight among adults aged 60 or older in India. Methods: We used data from the 2017–2018 Longitudinal Aging Study in India. The sample size was 27,902 adults aged 60 years and above. We distinguished between smoking and smokeless tobacco use to examine how they may independently contribute to the outcome, while food insecurity was measured using the four-item version of the Food Insecurity Experience scale. Multivariable logistic regressions were conducted to assess the impact of tobacco use and food insecurity on the outcome. Additionally, we tested interactions between tobacco use and education, as well as between tobacco use and wealth. Results: The prevalence of underweight was 27% in the study population. Older adults who used smoking tobacco were twice more likely to be underweight than non-users (OR = 2.07, 95% CI = 1.79 to 2.40, p &lt; 0.001), controlling for other confounders. The positive association between smokeless tobacco use and underweight was weaker but still significant (OR = 1.26, 95% CI = 1.11 to 1.42, p &lt; 0.001). Food-insecure older adults were also more likely to be underweight (OR = 1.27, 95% CI = 1.10 to 1.48, p &lt; 0.001). Other risk factors of underweight included males, rural residents, lower socioeconomic status (in terms of education, wealth, and caste), chewing disability, poor self-rated health, chronic lung disease, and tuberculosis. Interestingly, tobacco use moderated the relationship between wealth and underweight, such that smokers are more likely to be underweight as they become more affluent. Conclusions: Tobacco use and food insecurity have adverse implications on the nutritional status of the older persons in developing countries such as India. More targeted tobacco cessation measures and active food assistance programs for older adults are warranted to improve the overall health status of the older demographic.

Different antinuclear antibody subgroups of anti-melanoma differentiation-associated gene 5-positive dermatomyositis had variability in clinical presentation: a multicentre retrospective cohort study

IntroductionThis study aimed to investigate the association between ANA and clinical characteristics as well as prognosis in a cohort of patients with anti-MDA5+ DM.Material and methodsWe conducted a systematic retrospective study of medical records from Nanjing Medical University myositis associated interstitial lung disease (ILD) contort.ResultsA total of 246 patients with anti-MDA5+ DM were enrolled in this study, with 28.5% males and 71.5% females. The median age was 53.0 years, the median disease duration was 2 months, and the median follow-up period was 12.0 months. ANA positivity rate at baseline was 52.4% in anti-MDA5+ DM patients. The ANA-positive group showed significantly higher positivity rates of anti-Ro52 antibodies (72.9% vs 54.7%, p=0.003) and anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies (9.3% vs 2.6%, p=0.033) compared to the ANA-negative group, but lower ALT levels [39.0 (21.5, 79.3) vs 51.3 (36.5, 95.8), p=0.006].In a subgroup analysis of the ANA-positive group, MDA5+++ patients had a higher incidence of RPILD compared to the MDA5+ group (P=0.028). In the ANA negative subgroup analysis, MDA5+++ patients had a higher mortality rate and worse prognosis compared to the MDA5+ group (P=0.026). Multivariate COX regression analysis showed that elevated LDH levels and the presence of rapidly progressive interstitial lung disease (RPILD) were associated with poor prognosis in ANA-negative anti-MDA5+ DM patients [hazard ratios of 1.002 (95% CI 1.001, 1.003, P = 0.020) and 13.694 (95% CI 15.032, 37.267, P &lt; 0.001), respectively].ConclusionsANA is frequently found in patients with anti-MDA5+ DM. High titres of anti-MDA5 antibodies are associated with mortality and RPILD.

Phagocytic activity of neutrophil blood granulocytes in children with chronic non-specific lung diseases with post-inflammatory pneumofibrosis

One of the reasons for the development of chronic forms of lung diseases and pneumofibrosis as a pathological outcome of this inflammation may be an insufficient immune response. The key position belongs to neutrophilic granulocytes. Given the importance and renewed interest in neutrophils as tools for regulating immunity, leading to the progression of the fibrous process in children with CKD is an urgent problem. The purpose of the study was to study the phagocytic activity of blood neutrophils as an important component of innate immunity in patients with CNLD. Seventy children with CNLD with focal or segmental post-inflammatory pulmonary fibrosis were examined. Of these, 27 were children with progression of PPF (main group) and 43 children with PPF without progression (comparison group). The controls were the indicators of 23 healthy children, comparable by gender and age. The studies were carried out during clinical remission. The phagocytic activity of neutrophils (PНAN), phagocytic number (PN), spontaneous and stimulated NBT test were determined. The stimulation index of the NBT test (NBTst-NBTsp) was calculated. The mitochondrial membrane potential was determined using a BD FACS Calibur cytometer (USA) (BD Pharmigen, USA). PN in children with chronic heart disease with progressive PF was significantly reduced in comparison with patients in the comparison group and with the control group. The PHAN in children with CKD in both groups was within the standard values, however, it was lower than in the control group. The activity of the spontaneous HBT test in children of the main group was 1.7 times higher than in children in the comparison group and 3 times higher than in children from the control group. However, the stimulation index in the main group was significantly lower than in the control group. An increase in cells with a reduced membrane potential of granulocyte mitochondria was revealed in children of the main group compared with the control group. Children with CKD with the progression of fibrosis processes develop changes in the functional and metabolic activity of peripheral blood neutrophils typical for an inflammatory reaction, characterized by an increase in oxygen-dependent and a decrease in phagocytic cell activity.

A IMPORTÂNCIA DOS CUIDADOS ODONTOLÓGICOS EM PACIENTES INTERNADOS EM UNIDADE DE TERAPIA INTENSIVA

Hospitalized patients, specifically in ICUs, are unable to perform daily oral hygiene on their own, and are therefore more susceptible to developing more diseases if their oral cavity is not adequate, which can further aggravate their systemic condition. The objective of the study is to highlight the relevance of dental care in patients hospitalized in ICUs, exploring the main forms of action of the dentist and proposing preventive, diagnostic and therapeutic measures. The methodology was based on a bibliographic review, using articles from the SciELO, PubMed and BVS databases, published between 2014 and 2024. Complete and relevant articles for the topic were considered, while incomplete, duplicated or out-of-time texts were excluded. The reviewed literature highlights the connection between oral health and the prevention of systemic complications, such as heart and lung diseases. This study indicates that the presence of a dentist in multidisciplinary teams in ICUs is essential to prevent oral complications that can worsen the systemic health of patients in addition to prolonging the length of hospital stay.

Immunological characteristics of bronchoalveolar lavage fluid and blood across connective tissue disease-associated interstitial lung diseases

Interstitial lung disease (ILD) is a serious complication of connective tissue diseases (CTDs). The heterogeneity of ILDs reflects differences in pathogenesis among diseases. This study aimed to clarify the characteristics of CTD-ILDs via a detailed analysis of the bronchoalveolar lavage fluid (BALF) and blood immune cells. BALF and blood samples were collected from 39 Japanese patients with newly diagnosed ILD: five patients with Sjögren’s syndrome (SS), eight patients with dermatomyositis (DM), six patients with rheumatoid arthritis (RA), six patients with systemic sclerosis, four patients with anti-neutrophil cytoplasmic antibody-associated vasculitis, and 10 patients with idiopathic interstitial pneumonia. We performed single-cell RNA sequencing to analyze the gene expression profiles in these patients’ immune cells. In patients with SS, B cells in the BALF were increased and genes associated with the innate and acquired immunity were enriched in both the BALF and blood. In contrast, patients with DM showed an upregulation of genes associated with viral infection in both the BALF and blood. In patients with RA, neutrophils in the BALF tended to increase, and their gene expression patterns changed towards inflammation. These disease-specific characteristics may help us understand the pathogenesis for each disease and discover potential biomarkers.

Different risk and protective factors predict change of planning ability in middle versus older age

Age-related cognitive decline has become an increasingly relevant public health issue. However, risk and protective factors of cognitive decline have yet to be investigated prospectively taking into account genetic, lifestyle, physical and mental health factors. Population-based data from middle-aged (40 to 59 years; N = 2,764) and older individuals (60 to 80 years; N = 1,254) were drawn from a prospective community cohort study using the Tower of London (TOL) planning task. Assessments were repeated at a 5-year interval to investigate age-related changes in planning performance and to determine the impact of risk and protective factors. Planning performance improved in middle-aged, but declined in older participants over 5 years. SNPs affecting the dopamine system (COMT, DRD2) and APOE polymorphisms differentially predicted cognitive performance in older vs. middle-aged individuals. For older individuals, high alcohol consumption, antidepressant medication and living without a partner had additional negative predictive power on cognition. In contrast, undiagnosed hypertension, no obstructive lung disease, and fewer years of education predicted cognitive decline in the middle-aged group. The results inform screening for individuals particularly vulnerable to cognitive decline and interventions (e.g., focusing on lifestyle factors) to help maintain cognitive performance into old age.

Quantification of autoantibodies using a luminescent profiling method in autoimmune interstitial lung disease

Autoantibodies are important for the diagnosis of autoimmune interstitial lung disease (ILD). Standard immunoassays have limitations, including their qualitative nature and/or a narrow dynamic range of detection, hindering the usefulness of autoantibodies as biomarkers of disease activity. Here, the luciferase immunoprecipitation system (LIPS) was evaluated for measuring myositis-specific and other lung-related autoantibodies in 25 subjects with idiopathic inflammatory myopathies (IIM), 26 with Sjögren’s disease (SjD), and 10 healthy volunteers. LIPS detected a broad dynamic range of autoantibodies, to MDA5, Jo-1, PL12, KS, U1-70K, and Ro52, and matched seropositivity status with established immunoassays. Robust anti-MDA5 autoantibodies in four IIM-ILD patients had a median value of 1,134,000 LU (IQR 473,000-2,317,000), which was 500 times higher than in 21 seronegative IIM patients. Markedly elevated anti-Jo-1 autoantibodies in five IIM-ILD patients demonstrated a median value of 1,177,000 LU (IQR: 604,000-2,520,000), which was 1000-fold higher than in seronegative patients. Robust anti-Ro52 and other anti-tRNA-synthetase autoantibodies were detected in a subset of IIM-ILD subjects. In SjD, only anti-U1-70K and KS autoantibodies were identified in ILD patients with a prevalence of 30% and 20%, respectively. In longitudinal samples of five IIM-ILD patients, anti-Jo-1 autoantibody levels paralleled clinical improvement of lung function. LIPS can accurately quantify autoantibody levels as biomarkers for treatment response in patients with autoimmune ILD.

Future Considerations and Areas for Innovation for Pulmonary Rehabilitation in Chronic Obstructive Lung Disease Patients.

Pulmonary rehabilitation is an effective therapy that improves day-to-day symptoms and quality of life in patients with chronic obstructive pulmonary disease. In this review, we look at the role of virtual programs, implementation of artificial intelligence, emerging areas of improvement within the educational components of programs, and the benefit of advanced practice providers in directorship roles.

Effect of the Covid-19 pandemic on hospitalizations for non-Covid-19-pneumonia and exacerbations of chronic obstructive pulmonary diseases in Switzerland: comparison of national data between 2020/2021 and 2015–2019

BackgroundProtective measures applied during the Covid-19 pandemic had a marked impact on the incidence of pneumonia. However, systematic data are lacking for hospitalizations for pneumonia and acute exacerbations of chronic obstructive lung diseases (AECOPD) not caused by SARS-CoV-2 in Switzerland. We aimed to compare the incidences of hospitalization for these entities between 2020/2021 and prepandemic years.MethodsThis retrospective study examined all nationwide hospitalizations for non-Covid-19-pneumonia and AECOPD listed as primary diagnoses based on ICD-10 codes between 2015 and 2021 in a publicly available hospitalization database of the Swiss Federal Statistical Office. Hospitalizations for acute coronary syndrome (ACS) and stroke were used as controls. Changes of monthly incidences of hospitalizations, length of stay (LOS) and mortality were compared between 2020/2021 and the average of 2015–2019.ResultsThe incidences of hospitalizations for AECOPD and for pneumonia showed seasonal variations from 2015 to 2019 followed by significant and almost identical decreases in 2020/2021 (incidence rate ratio [IRR] 0.59, 95% CI: 0.45–0.77, p < 0.001, and IRR: 0.62, 95% CI: 0.52–0.74, p < 0.001, respectively). Hospital-mortality was slightly higher in 2020/2021 for AECOPD (2015–2019: 3.8%; 2020/2021: 4.2%, odds ratio [OR] 1.24, 95% CI: 1.07–1.44, p = 0.004) and for pneumonia (2015–2019: 4.5%, 2020/2021: 4.6%, odds ratio [OR] 1.17, 95% CI: 1.07–1.28, p < 0.001). Median LOS slightly decreased for AECOPD (2015–2019: 8 [IQR: 5–14] days; 2020/2021: 7 [IQR: 4–13] days, Wilcoxon test: p < 0.001) but slightly increased for pneumonia (2015–2019: 7 [IQR: 4–11] days; 2020/2021: 7 [IQR: 4–13] days, Wilcoxon test: p < 0.001). Throughout 2020/2021, there were no significant fluctuations observed in the incidences of ACS and stroke. (IRR: 0.98, 95% CI: 0.83–1.16, p = 0.810, IRR: 0.96, 95% CI: 0.81–1.14, p = 0.636, respectively).ConclusionThe first two years of the Covid-19 pandemic showed a marked decrease in incidences in AECOPD and non-Covid-19 pneumonia hospitalizations in Switzerland. It is likely that this effect is associated with the society-based, at first vigorous, social distancing measures.

Long-term outcome of interstitial lung disease in patients with primary Sjögren's syndrome: a retrospective observational study.

Interstitial lung disease (ILD) is a potentially serious but underdiagnosed manifestation of primary Sjögren's syndrome (pSS). This observational study investigated the prevalence and clinical course of ILD in pSS, together with prognostic factors. A multicenter, retrospective longitudinal study was performed using findings from baseline and follow-up pulmonary function tests and chest computed tomography. Predisposing factors for the development of ILD and acute exacerbation (AE) were identified using a logistic regression model. The risk factors for a significant decline of pulmonary function were determined by the Cox proportional hazard model. A total of 1,306 patients with pSS were included in this study (female, 98%; mean age, 54 years). Among them, 79 patients with pSS were comorbid with ILD. ILD was more frequently found in male, older patients. Nonspecific interstitial pneumonia was the most prevalent imaging pattern in pSS-ILD (51%), followed by usual interstitial pneumonia (22%). At diagnosis with pSS-ILD, 54% of patients had restrictive pulmonary function, and 41% of patients initiated pharmacological treatment. During the median 4-year follow-up period, AE, a significant decline in pulmonary function, and death occurred in 19%, 29%, and 9% of patients with pSS-ILD, respectively. The neutrophil-to-lymphocyte ratio (NLR) increased 3 months prior to AE, and it was associated with AE. Older age at pSS-ILD diagnosis was a prognostic factor for a significant decline in pulmonary function. ILD accounted for 6% of the comorbidity of pSS. AE was associated with a significant decline in pulmonary function, and the NLR may predict AE.

The Pores of Kohn, an Overlooked Pulmonary Structure: A Review

Many studies from the early 20th century on the significance of the pores of Kohn were assessed based on the pathogenesis and pathology of pneumococci pneumonia occurring in man. The pneumococci were carried in the edema fluid directly from alveolus to alveolus through the pores of Kohn and from bronchiole to bronchiole as a result of repeated aspirations, aided by breathing, coughing, and gravity. With the emerging minimally invasive and non-invasive techniques experimentations and the current medications; tackling exacerbations and improving the pulmonary function in various lung diseases remains a dilemma for clinicians and researchers. In this article, we aim to review specifically the pores of Kohn as this is the portal for the spread of infection but also lung recruitment during breathing.

Empowering Healthcare: TinyML for Precise Lung Disease Classification

Respiratory diseases such as asthma pose significant global health challenges, necessitating efficient and accessible diagnostic methods. The traditional stethoscope is widely used as a non-invasive and patient-friendly tool for diagnosing respiratory conditions through lung auscultation. However, it has limitations, such as a lack of recording functionality, dependence on the expertise and judgment of physicians, and the absence of noise-filtering capabilities. To overcome these limitations, digital stethoscopes have been developed to digitize and record lung sounds. Recently, there has been growing interest in the automated analysis of lung sounds using Deep Learning (DL). Nevertheless, the execution of large DL models in the cloud often leads to latency, dependency on internet connectivity, and potential privacy issues due to the transmission of sensitive health data. To address these challenges, we developed Tiny Machine Learning (TinyML) models for the real-time detection of respiratory conditions by using lung sound recordings, deployable on low-power, cost-effective devices like digital stethoscopes. We trained three machine learning models—a custom CNN, an Edge Impulse CNN, and a custom LSTM—on a publicly available lung sound dataset. Our data preprocessing included bandpass filtering and feature extraction through Mel-Frequency Cepstral Coefficients (MFCCs). We applied quantization techniques to ensure model efficiency. The custom CNN model achieved the highest performance, with 96% accuracy and 97% precision, recall, and F1-scores, while maintaining moderate resource usage. These findings highlight the potential of TinyML to provide accessible, reliable, and real-time diagnostic tools, particularly in remote and underserved areas, demonstrating the transformative impact of integrating advanced AI algorithms into portable medical devices. This advancement facilitates the prospect of automated respiratory health screening using lung sounds.

Downstream Effects of Market Changes on Inhalers: Impacts on Individuals With Chronic Lung Disease.

COPD and asthma are two of the most common chronic lung diseases, affecting over 545 million people globally and 34 million in the United States. Annual health care costs related to chronic lung disease are estimated at €380 billion in the European Union, and $24-$50 billion in the United States averaging to $4,000 in out-of-pocket costs per person in the U.S. A full-text literature search was conducted for English publications between January 1, 2005-March 18, 2024. It returned over 5,000 publications that were further narrowed using key search words, resulting in 172 peer-reviewed articles. Using their experience and subject expertise, the authors further narrowed the peer-reviewed articles to 55 that were in their opinion relevant. Also, 38 recently published industry reports and news articles specific to downstream effects of inhaler market changes and the future impact were included. The literature suggests that individuals with chronic lung disease face increased challenges with access to inhaled medication due to rising medication costs, discontinuation of branded medications, introduction of generic medications not covered by insurance, exclusionary preferred drug list tactics that force health care providers into non-medical switching of medication or devices, and ongoing medication shortages. Providers experience ongoing hurdles in prescribing appropriate inhaled medications for individuals with chronic lung disease, including increased time and costs spent on administrative tasks due to inhaler denials, a loss of patient trust, and limits on their ability to prescribe appropriate inhaled medication for individuals with chronic lung disease.

Potential mechanisms of interstitial lung disease induced by antibody-drug conjugates based on quantitative analysis of drug distribution.

Antibody-drug conjugates (ADCs) are a rapidly advancing category of therapeutic agents with notable anti-cancer efficacy. However, the emergence of interstitial lung disease (ILD) as a severe ADC-associated adverse event highlights the need to better understand the underlying mechanisms. In this study, xenograft model mice with tumors expressing different levels of the trophoblast antigen 2 (TROP2) were generated by subcutaneously transplanting the various TROP2-expression cancer lines. The mice received different doses of TROP2-eribulin, a novel TROP2-targeting ADC, composed of an anti-TROP2 antibody and the eribulin payload, joined by a cleavable linker. The concentration and distribution of TROP2-eribulin, as well as the pharmacokinetics of eribulin release, were assessed in tumor and lung tissues. Analysis of tumor tissue showed that the concentration of released eribulin was approximately 10-fold higher in NCI-H2110 (high TROP2 expression) than in A549 (low TROP2 expression), while analysis of lung tissue showed that TROP2-eribulin was distributed in lung tissue in a dose-dependent manner of TROP2-eribulin regardless of TROP2 expression, with significantly more eribulin released in the high-dose group than in the other dose groups (P < 0.05). Immunofluorescence assay analysis showed that TROP2-eribuilin localized to alveolar macrophages. In the analysis using human- leukemia monocytic cell, the concentration of eribulin released from TROP2-eribuilin was significantly reduced by the use of an Fc receptor inhibitor (P < 0.05). These results revealed that Fcγ-receptor-mediated uptake by alveolar macrophages releases cytotoxic payload into lung tissue, helping to clarify the pathogenesis of ADC-induced ILD.