Lung Disease Research Articles

New insights into crosstalk between Nrf2 pathway and ferroptosis in lung disease

AbstractFerroptosis is a distinctive process of cellular demise that is linked to amino acid metabolism, lipid oxidation, and iron oxidation. The ferroptosis cascade genes, which are closely associated with the onset of lung diseases, are among the regulatory targets of nuclear factor erythroid 2-related factor 2 (Nrf2). Although the regulation of ferroptosis is mostly mediated by Nrf2, the precise roles and underlying regulatory mechanisms of ferroptosis and Nrf2 in lung illness remain unclear. This review provides new insights from recent discoveries involving the modulation of Nrf2 and ferroptosis in a range of lung diseases. It also systematically describes regulatory mechanisms involving lipid peroxidation, intracellular antioxidant levels, ubiquitination of Nrf2, and expression of FSP1 and GPX4. Finally, it summarises active ingredients and drugs with potential for the treatment of lung diseases. With the overarching aim of expediting improvements in treatment, this review provides a reference for novel therapeutic mechanisms and offers suggestions for the development of new medications for a variety of lung disorders.

An Efficient One-Dimensional Texture Representation Approach for Lung Disease Diagnosis

The remarkable increase in published medical imaging datasets for chest X-rays has significantly improved the performance of deep learning techniques to classify lung diseases efficiently. However, large datasets require special arrangements to make them suitable, accessible, and practically usable in remote clinics and emergency rooms. Additionally, it increases the computational time and image-processing complexity. This study investigates the efficiency of converting the 2D chest X-ray into one-dimensional texture representation data using descriptive statistics and local binary patterns, enabling the use of feed-forward neural networks to efficiently classify lung diseases within a short time and with cost effectiveness. This method bridges diagnostic gaps in healthcare services and improves patient outcomes in remote hospitals and emergency rooms. It also could reinforce the crucial role of technology in advancing healthcare. Utilizing the Guangzhou and PA datasets, our one-dimensional texture representation achieved 99% accuracy with a training time of 10.85 s and 0.19 s for testing. In the PA dataset, it achieved 96% accuracy with a training time of 38.14 s and a testing time of 0.17 s, outperforming EfficientNet, EfficientNet-V2-Small, and MobileNet-V3-Small. Therefore, this study suggests that the dimensional texture representation is fast and effective for lung disease classification.

Perception of Gratitude During an Online Mindfulness-Based Intervention (eMBI) in Patients with Interstitial Lung Disease in Brazil: An Exploratory Qualitative Study

Perception of Gratitude During an Online Mindfulness-Based Intervention (eMBI) in Patients with Interstitial Lung Disease in Brazil: An Exploratory Qualitative Study

Hyaluronan in COVID-19: a matrix for understanding lung disease

ABSTRACT The polysaccharide hyaluronan (HA) is an important component of lung extracellular matrix that increases following infection with influenza or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hellman et al. (U. Hellman, E. Rosendal, J. Lehrstrand, J. Henriksson, et al., mBio 15:e01303-24, https://doi.org/10.1128/mbio.01303-24 ) show that fragmented HA accumulates in the lungs of coronavirus disease 2019 (COVID-19) patients, with systemic levels of HA being associated with reduced lung function 3–6 months after infection. This study provides novel insights into HA’s role in COVID-19 pathology and its potential utility as a biomarker for disease severity. However, much remains to be understood about the lung HA matrix in COVID-19 and how it compares to other lung conditions. In particular, the role of HA-binding proteins in organizing HA into a crosslinked network is yet to be fully determined at a molecular level. This knowledge is crucial in understanding the inter-relationships between the structure of the HA matrix and the regulation of the immune response, and thus our ability to target HA therapeutically for improved outcomes in COVID-19.

Protocol and research program of the European registry and biobank for interstitial lung diseases (eurILDreg)

Abstract Background and Aims Interstitial lung diseases (ILDs), encompassing both pediatric and adult cases, present a diverse spectrum of chronic conditions with variable prognosis. Despite limited therapeutic options beyond antifibrotic drugs and immunosuppressants, accurate diagnosis is challenging, often necessitating invasive procedures that may not be feasible for certain patients. Drawn against this background, experts across pediatric and adult ILD fields have joined forces in the RARE-ILD initiative to pioneer novel non-invasive diagnostic algorithms and biomarkers. Collaborating with the RARE-ILD consortium, the eurILDreg aims to comprehensively describe different ILDs, analyze genetically defined forms across age groups, create innovative diagnostic and therapeutic biomarkers, and employ artificial intelligence for data analysis. Methods The foundation of eurILDreg is built on a comprehensive parameter list developed and adopted by clinical experts, encompassing over 1,800 distinct parameters related to patient history, clinical examinations, diagnosis, lung function and biospecimen collection. This robust dataset is further enriched with daily assessments captured through the patientMpower app, including handheld spirometry and exercise tests, conducted on approximately 350 patients over the course of a year. This approach involves app-based daily assessments of quality of life, symptom tracking, handheld spirometry, saturation measurement, and the 1-min sit-to-stand test (1-STST). Additionally, pediatric data from the ChILD-EU registry will be integrated into the RARE-ILD Data Warehouse, with the ultimate goal of including a total of 4.000 ILD patients and over 100.000 biospecimen. Discussion The collaborative efforts within the consortium are poised to streamline research endeavors significantly, promising to advance patient-centered care, foster innovation, and shape the future landscape of interstitial lung disease research and healthcare practices. Trial Registration EurILDreg is registered in the German Clinical Trials Register (DRKS 00028968, 26.07.2022), and eurIPFreg is registered in ClinicalTrials.gov (NCT02951416).

Real-world incidence of and risk factors for abemaciclib-induced interstitial lung disease in Japan: a nested case–control study of abemaciclib-induced interstitial lung disease (NOSIDE)

Real-world incidence of and risk factors for abemaciclib-induced interstitial lung disease in Japan: a nested case–control study of abemaciclib-induced interstitial lung disease (NOSIDE)

A Call to Action for Global Solutions to Air Quality Crisis: Urgent Actions and Innovative Solutions Needed

ABSTRACT Air pollution, specifically smog, has become a prevalent concern worldwide due to its association with various health risks including stroke, heart disease, lung disease, lower respiratory disorders, and cancer. The excessive use of fossil fuels and the rapidly increasing population have led to the rise in air pollution, which also increases the risk of other ailments such as diabetes and negatively impacts cognitive development in children as well as mental health. According to the World Health Organization, almost 7 million people die each year due to air pollution. According to the recent reports by the Swiss organization (IQAir) on October 22nd, 2024, accessed at (https://www.iqair.com) Lahore in Pakistan, Delhi in India, Kinshasa in Democratic Republic of the Congo, Milano in Italy, Belgrade in Serbia, Jakarta in Indonesia and Karachi in Pakistan have been identified as the top seven cities with the highest US Air Quality Index (AQI). The rising levels of air pollution pose significant health risks globally, necessitating immediate action from governments and communities. Implementing effective policies, investing in clean technologies, and fostering international collaboration are essential to mitigate the impacts of air quality deterioration on public health and the environment.

Development of Imaging Complexity Biomarkers for Prediction of Symptomatic Radiation Pneumonitis in Patients with Non-Small Cell Lung Cancer, Focusing on Underlying Lung Disease

Objectives: We aimed to develop imaging biomarkers to predict radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients undergoing thoracic radiotherapy. We hypothesized that measuring morphometric complexity in the lung using simulation computed tomography may provide objective imaging biomarkers for lung parenchyma integrity, potentially forecasting the risk of RP. Materials and Methods: A retrospective study was performed on medical records of 175 patients diagnosed with NSCLC who had received thoracic radiotherapy. Three indices were utilized to measure the morphometric complexity of the lung parenchyma: box-counting fractal dimension, lacunarity, and minimum spanning tree (MST) fractal dimension. Patients were dichotomized into two groups at median values. Cox proportional hazard models were constructed to estimate the hazard ratios for grade ≥ 2 or grade ≥ 3 RP. Results and Conclusions: We found significant associations between lung parenchymal morphometric complexity and RP incidence. In univariate Cox-proportional hazard analysis, patients with a lower MST fractal dimension had a significantly higher hazard ratio of 2.296 (95% CI: 1.348–3.910) for grade ≥ 2 RP. When adjusted for age, sex, smoking status, category of the underlying lung disease, category of radiotherapy technique, clinical stage, histology, and DLCO, patients with a lower MST fractal dimension showed a significantly higher hazard ratio of 3.292 (95% CI: 1.722–6.294) for grade ≥ 2 RP and 7.952 (95% CI: 1.722 36.733) for grade ≥ 3 RP than those with a higher MST fractal dimension. Patients with lower lacunarity exhibited a significantly lower hazard ratio of 0.091 (95% CI: 0.015–0.573) for grade ≥ 3 RP in the adjusted model. We speculated that the lung tissue integrity is captured by morphometric complexity measures, particularly by the MST fractal dimension. We suggest the MST fractal dimension as an imaging biomarker for predicting the occurrence of symptomatic RP after thoracic radiotherapy.

Inter-cohort shifts in chronic disease, dementia, and mortality

ABSTRACT Previous work using U.S. data has identified generational shifts, reflected in inter-cohort changes, in the incidence and prevalence of diseases in older ages. This study extends previous findings to England by examining similar results in memory complaints, heart conditions, stroke, diabetes, lung disease, and cancer using data from the English Longitudinal Study of Ageing (ELSA). We fit Cox proportional hazard models to the first eight waves (2002–2016) of the ELSA sample (n = 18,528). In addition to exploring shifts in disease incidence we also examine shifts in disease mortality. Both general and sex-related differences are examined. Disease incidence has increased for later-born cohorts in England, replicating similar trends in the U.S. Not all diseases showed differences between men and women, but when differences were identified, women had lower risks for disease. In comparison to the U.S. sample, disease trends in England are more negative (i.e. accelerated failure times) for more recently born cohorts. These results showing increasing incidence of disease among the later-born cohorts suggest the possibility of increased disease burden in coming years.

Malignancies in patients with psoriasis during and after biological therapy: A single-center experience.

Over a 14-year period from 2010 to 2023, we treated 86 psoriasis patients with various biological agents at Asahikawa City Hospital, and 12 malignancies occurred in 11 of the patients. The numbers of malignancies by organ were as follows: four urogenital, three hematological, two gastrointestinal, one breast, one thyroid, and one lung. In two patients without cancer-related symptoms, elevated serum Krebs von den Lungen-6 levels led to the detection of intrahepatic cholangiocarcinoma or thyroid cancer, and they did not have interstitial lung disease. Dermatologists should be aware of the increased incidence of malignancy in patients with psoriasis requiring treatment with biologics.

Multipotent mesenchymal stromal cell therapy for a neonate with congenital diaphragmatic hernia and adhesive small bowel obstruction

Background. In the last decade, therapy using multipotent mesenchymal stromal cells (MSCs) has offered hope for regenerating the lungs of preterm babies with chronic lung disease. Due to similar disease mechanisms, it is logical to explore the potential impact of MSC therapy on pulmonary hypoplasia in congenital diaphragmatic hernia. Furthermore, MSCs may also contribute to the regeneration of the intestines affected by adhesive small bowel obstruction in patients with congenital diaphragmatic hernia. Case presentation. A female newborn, delivered at 32 weeks and six days gestational age, was diagnosed with a left congenital diaphragmatic hernia. After surgical repair and respiratory/nutritional support for 39 days, she was still dependent on a ventilator and total parenteral nutrition. Two MSC treatments were given a week apart: 10 million cells/kg intratracheally and 5 million cells/kg intravenously. She was extubated, and her enteral nutrition improved after the treatment. No side effects were detected. We present the first documented case using MSCs derived from the umbilical cord to simultaneously treat pulmonary hypoplasia and adhesive small bowel obstruction of congenital diaphragmatic hernia. Conclusion. Although MSC treatment is very promising for pulmonary hypoplasia and adhesive small bowel disease of congenital diaphragmatic hernia, much more needs to be learned about potential side effects, appropriate dosage, and the optimal method of administration.

Non-infectious mixed cryoglobulinemia as a new clinical presentation of mutation in the gene encoding coatomer subunit alpha: a case report of two adult sisters

Cryoglobulinemia is a rare disease characterized by the presence of cryoglobulins in the blood serum. It is usually caused by autoimmune, lymphoproliferative, or infectious factors. The pathogenesis of cryoglobulinemia is not well understood, therefore, genetic testing is very important. We present the case of two adult sisters with different clinical phenotypes of non-infectious cryoglobulinemic vasculitis associated with a rare genetic variant [(Hg38) 1:160323529 C>G, NP_004362.2:p.(Gly203Ala)]. One of the sisters suffered from essential mixed cryoglobulinemia, while the other suffered from cryoglobulinemia associated with systemic connective tissue disease. In both cases, genetic tests revealed a variant in the COPA gene, encoding coatomer subunit alpha. Mutations in the COPA gene are associated with COPA syndrome, an autoimmune interstitial lung, joint, and kidney monogenic disease, found mainly in children. Only 15 pathogenic COPA variants have been reported thus far which suggests that the full spectrum of disease manifestations remains unknown. Ours is the first report of the association of the COPA gene with non-infectious cryoglobulinemic vasculitis in adults. This unexpected finding may direct research into the pathogenesis of cryoglobulinemia and new treatment strategies for this rare disease.

Discovery of Selective PDE1 Inhibitors with Anti-pulmonary Fibrosis Effects by Targeting the Metal Pocket.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with no ideal drugs. Our previous research demonstrated that phosphodiesterase 1 (PDE1) could be a promising target for the treatment of IPF. However, only a few selective PDE1 inhibitors are available, and the mechanism of recognition between inhibitors and the PDE1 protein is not fully understood. This study carried out a step-by-step optimization of a dihydropyrimidine hit Z94555858. By targeting the metal pocket of PDE1, a lead compound 3f was obtained, exhibiting an IC50 value of 11 nM against PDE1, moderate selectivity over other PDEs, and significant anti-fibrotic effects in bleomycin-induced pulmonary fibrosis rats. The structure-activity relationship study aided by molecular docking revealed that forming halogen bonds with water in the metal pocket greatly enhanced the PDE1 inhibition, providing a novel strategy for further rational design of PDE1 inhibitors.

Functional Outcome after Clinical Recovery from Moderate to Critical COVID-19 among Patients Admitted to the Philippine General Hospital: A Prospective Cohort Study

Background and Objective. COVID-19 is a novel disease primarily affecting the respiratory system. Of those infected, approximately 20% require management in a hospital-setting which may lead to deconditioning. Measures implemented to control spread of the virus also restricted mobility both in the hospital and community setting. The goal of this study was to describe the patient characteristics (age, sex, comorbidities), hospitalization (length of hospital stay, ICU stay, referral to Rehabilitation Medicine), and long-term functional outcome of patients who have clinically recovered from moderate to critical COVID-19 in terms of participation in activities of daily living. Methods. This was a descriptive prospective cohort study conducted at a tertiary government hospital with participant recruitment from September 2020 to February 2021 consisting of clinically recovered adult patients managed as COVID-19 Confirmed via rRT-PCR with moderate, severe, or critical risk status. Descriptive statistics were obtained and multiple regression analysis was done to determine associations between patient demographics and their Barthel Index Scores on follow-up at discharge, one month post-discharge, and six months post-discharge. Results. A total of 63 patients were recruited to our study with an average age of 52.4 years. More recovered patients had fulfilled the criteria of moderate illness (46%), with the most common comorbidity being chronic lung disease (42.1%) and diabetes (42.1%). Almost all had total independence pre-morbidly with better baseline functional scores for the COVID-19 severe population. Majority of the patients (63.5%) were not referred for Rehabilitation services. Across all patients, Barthel Index Score at discharge indicated a significant decline from slight dependence to moderate dependence in performing activities of daily living with the pre-morbid status significantly predicting scores at discharge (β = 0.621, p = 0.001) on multiple regression analysis. Patient demographics, hospitalization and ICU stay and outcome, and referral to Rehabilitation Medicine were not found to be significant factors. In the course of follow up, a high dropout rate was observed across the population and by the end of the study, 57.1% of the participants were alive while among those lost to follow up, 20.6% had expired and the remaining 22.2% had an unknown status. Conclusion. COVID-19 significantly affects the functional outcome of patients in terms of activities of daily living as measured by the Barthel Index. Preliminary data gathered from our study and the high dropout rate supports the need for better follow-up and selecting a tool that is better able to describe the non-demographic factors affecting functionality and participation in activities of daily living.

Pulmonary manifestations of juvenile vs. adult systemic sclerosis: insights into pathophysiological and clinical features.

Juvenile systemic sclerosis (jSSc), the pediatric counterpart of systemic sclerosis (SSc), is a rare autoimmune disorder characterized by vasculopathy and fibrotic disorders. It ranks among the rheumatologic diseases with the highest rates of morbidity and mortality, predominantly impacting females. Although a universally accepted classification for jSSc remains elusive, a provisional classification proposed in 2007 integrates major and minor criteria, reflecting the involvement of diverse organs and tissues. Pulmonary manifestations are relatively common in jSSc, occurring in 36% to 55% of cases. Particularly lung complications include children s interstitial lung disease (chILD), pulmonary arterial hypertension (PAH) and nodules. The aim of this paper is to describe the main pulmonary manifestations of patients with jSSc in relation to SSc, highlighting fundamental pathophysiological, and clinical features based on the latest literature data.

Combined therapy with pirfenidone and nintedanib counteracts fibrotic silicosis in mice.

Pneumoconiosis, especially silicosis, is a prevalent occupational disease with substantial global economic implications and lacks a definitive cure. Both pneumoconiosis and idiopathic pulmonary fibrosis (IPF) are interstitial lung diseases, which share many common physiological characteristics. Because pirfenidone and nintedanib are approved to treat IPF, their potential efficacy as antifibrotic agents in advanced silicosis deserves further exploration. Thus, we aimed to evaluate the individual and combined effects of pirfenidone and nintedanib in treating advanced silicosis mice and elucidate the underlying mechanisms of their therapeutic actions via multiomics. We administered monotherapy or combined therapy of pirfenidone and nintedanib, with low and high doses, in silicosis established after 6weeks and evaluated lung function, inflammatory responses and fibrotic status. Additionally, we employed transcriptomic and metabolomic analyses to uncover the mechanisms underlying different therapeutic strategies. Both pirfenidone and nintedanib were effective in treating advanced silicosis, with superior outcomes observed in combination therapy. Transcriptomic and metabolomic analyses revealed that pirfenidone and nintedanib primarily exerted their therapeutic effects by modulating immune responses, signalling cascades and metabolic processes involving lipids, nucleotides and carbohydrates. Furthermore, we experimentally validated both monotherapy and combined therapy yielded therapeutic benefits through two common signalling pathways: steroid biosynthesis and purine metabolism. In conclusion, pirfenidone and nintedanib, either individually or in combination, demonstrate substantial potential in advanced silicosis. Furthermore, combined therapy outperformed monotherapy, even at low doses. These therapeutic benefits are attributed to their influence on diverse signalling pathways and metabolic processes.

Mitophagy-Enhanced Nanoparticle-Engineered Mitochondria Restore Homeostasis of Mitochondrial Pool for Alleviating Pulmonary Fibrosis.

Pulmonary fibrosis (PF) is an interstitial lung disease tightly associated with the disruption of mitochondrial pool homeostasis, a delicate balance influenced by functional and dysfunctional mitochondria within lung cells. Mitochondrial transfer is an emerging technology to increase functional mitochondria via exogenous mitochondrial delivery; however, the therapeutic effect on mitochondrial transfer is hampered during the PF process by the persistence of dysfunctional mitochondria, which is attributed to impaired mitophagy. Herein, we reported engineering mitochondria mediated by mitophagy-enhanced nanoparticle (Mito-MEN), which promoted synchronal regulation of functional and dysfunctional mitochondria for treating PF. Mitophagy-enhanced nanoparticles (MENs) were fabricated through the encapsulation of Parkin mRNA, and the electrostatic interaction favored MENs to anchor isolated healthy mitochondria for the construction of Mito-MEN. Mito-MEN increased the load of functional exogenous mitochondria by enhancing mitochondrial delivery efficiency and promoted mitophagy of dysfunctional endogenous mitochondria. In a bleomycin (BLM)-induced PF mouse model, Mito-MEN repaired mitochondrial function and efficiently relieved PF-related phenotypes. This study provides a powerful tool for synchronal adjustment of mitochondrial pool homeostasis and offers a translational approach for pan-mitochondrial disease therapies.

The HYdrocortisone for Bronchopulmonary Dysplasia Respiratory and Developmental (HYBRiD) outcomes study: protocol for a longitudinal cohort study.

Bronchopulmonary dysplasia (BPD) affects up to half of extremely preterm infants, and is associated with adverse long-term respiratory, neurodevelopmental, and educational sequelae and costly health service and family economic outcomes. The NICHD Neonatal Research Network Hydrocortisone for Bronchopulmonary Dysplasia (BPD) Trial evaluated the efficacy and safety of hydrocortisone treatment to prevent BPD in high-risk infants. The trial enrolled 800 very preterm infants with respiratory failure and followed the participants until 2 years corrected age to assess safety of the trial intervention. Longer-term impacts of hydrocortisone exposure and severity of BPD on functional outcomes of high-risk infants remain unknown. The HYdrocortisone for BPD Respiratory and Developmental (HYBRiD) Outcomes Study extends follow-up of all surviving children enrolled in the Hydrocortisone for BPD Trial until early school age. It aims to characterize the childhood functional motor, cognitive, academic, and pulmonary outcomes of this large, well-phenotyped trial cohort. Parents of surviving trial participants complete telephone questionnaires when their children are 3 and 4 years corrected age. A single in-person study visit takes place at early school age (5 years, 0 months to 7 years, 11 months corrected age). Children undergo a multidimensional assessment of functional outcomes and parents complete a battery of questionnaires. In 5 of 19 participating centers, respiratory mechanics are evaluated with impulse oscillometry. The HYBRiD Outcomes Study will be the largest and most comprehensive evaluation to date of the functional early school age outcomes of children with a history of severe neonatal lung disease and of children exposed to HC during infancy. This will substantially improve understanding of the longer-term implications of severe neonatal lung disease; provide data to facilitate the development of future randomized intervention trials in this population; and inform public policy by enhancing knowledge about school age resource requirements in children with a history of prematurity and lung disease. clinicaltrials.gov ID NCT01353313. Primary trial registration 5/11/11 modified to include followup through school age 12/13/17. This manuscript reflects version 3 of the trial manuscript, dated 10/12/2020.

Inhalation Exposure to Cross-linked Polyacrylic Acid Induces Pulmonary Disorders.

Organic polymers, widely used in food, daily necessities, and medicines, include cross-linked polyacrylic acid (CL-PAA), which has been reported to induce severe lung disease. While previous studies mainly used intratracheal instillation, our research focused on inhalation exposure to corroborate these findings. We conducted 5-day (short-term) and 13-week (subchronic) inhalation exposure studies with CL-PAA. In the short-term study, male F344 rats inhaled CL-PAA at 0.2, 2.0, or 20mg/m³ for 6hours/day over 5 days. Rats were dissected 3 days and 1 month post-exposure. In the subchronic study, rats inhaled CL-PAA at 0.2 or 2.0mg/m³ for 6hours/day, 5 days/week for 13 weeks, with dissections from 3 days to 6 months post-exposure. To investigate the mechanism of pulmonary disorders, an additional short-term study with 20mg/m³ CL-PAA included intraperitoneal injections of the antioxidant N-acetylcysteine (NAC) (200mg/kg) with dissection the day after exposure. Short-term exposure led to concentration-dependent increases in neutrophil influx, cytokine-induced neutrophil chemoattractant (CINC), total protein, lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in lung tissue. Histopathology showed concentration-dependent neutrophil infiltration. Subchronic exposure caused persistent increases in BALF total protein and lung HO-1, with ongoing neutrophil infiltration and fibrosis. NAC administration reduced neutrophils, total protein, LDH, and CINC in BALF, and HO-1 in lung tissue, improving histopathological findings. Inhalation of CL-PAA caused concentration-dependent lung inflammation and persistent fibrosis. The no observed adverse effect level (NOAEL) for chronic pulmonary disorders was 0.2mg/m³. Oxidative stress linked to CL-PAA-induced inflammation was mitigated by NAC administration.

Air Pollution and Interstitial Lung Disease.

This review article explores the multifaceted relationship between air pollution and interstitial lung diseases (ILDs), particularly focusing on idiopathic pulmonary fibrosis (IPF), the most severe form of fibrotic ILD. Air pollutants are mainly composed of particulate matter (PM), ozone (O3), nitrogen dioxide (NO2), carbon monoxide (CO), and sulfur dioxide (SO2). They are recognized as risk factors for several respiratory diseases. However, their specific effects on ILDs and related mechanisms have not been thoroughly studied yet. Emerging evidence suggests that air pollutants may contribute to the development and acute exacerbation of ILDs. Longitudinal studies have indicated that air pollution can adversely affect the prognosis of disease by decreasing lung function and increasing mortality. Lots of in vitro, in vivo, and epidemiologic studies have proposed possible mechanisms linking ILDs to air pollution, including inflammation and oxidative stress induced by exposure to air pollutants, which may induce mitochondrial dysfunction, promote cellular senescence, and disrupt normal epithelial repair processes. Despite these findings, effective interventions to mitigate effects of air pollution on ILD are not well established yet. This review emphasizes the urgent need to address air pollution as a key environmental risk factor for ILDs and calls for further studies to clarify its effects and develop preventive and therapeutic strategies.