Journal of Pulmonology and Respiratory Diseases
Open Access

Lung inflammation; Respiratory diseases; Cytokines; Immune response; COPD; Asthma; Treatment

Introduction

Lung inflammation is a central feature of many chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and interstitial lung diseases (ILDs). The persistence of inflammation in the lungs not only contributes to disease pathogenesis but also drives airway remodeling and fibrosis, resulting in impaired lung function and progressive morbidity [1]. Inflammation in the lungs is primarily initiated by environmental factors such as smoking, air pollution, infections, and allergens, which activate both innate and adaptive immune responses. This process involves the release of a wide array of pro-inflammatory cytokines, chemokines, and immune mediators that recruit and activate various immune cells, such as neutrophils, macrophages, T lymphocytes, and eosinophils [2]. In asthma, the inflammation is predominantly Th2-driven, characterized by the recruitment of eosinophils and the release of cytokines such as interleukins (IL-4, IL-5, IL-13). These cytokines promote airway hyperresponsiveness, mucus production, and smooth muscle contraction, leading to recurrent wheezing, breathlessness, and coughing [3]. In contrast, COPD is typically associated with neutrophil-driven inflammation, which results in tissue damage, emphysema, and airway narrowing. Chronic exposure to cigarette smoke or environmental pollutants is a key trigger for this inflammation. In ILDs, lung inflammation is followed by excessive fibrosis, primarily driven by transforming growth factor-beta (TGF-β), which leads to collagen deposition and scarring of the lung parenchyma [4]. Despite the extensive research into the mechanisms of lung inflammation, effective therapeutic strategies remain limited. While corticosteroids and bronchodilators provide symptomatic relief, they are often inadequate in halting disease progression or addressing the underlying inflammatory processes [5]. Newer biologic therapies targeting specific inflammatory mediators, such as monoclonal antibodies and Janus kinase inhibitors, are emerging as promising treatments. This review explores the pathophysiology of lung inflammation in respiratory diseases and evaluates the current and potential future therapeutic options.

Results

Recent studies have shed light on the mechanisms of lung inflammation in various respiratory diseases, revealing both shared and disease-specific pathways. In asthma, Th2 cytokines (IL-4, IL-5, and IL-13) are central to the inflammatory response. These cytokines drive the recruitment and activation of eosinophils, which contribute to airway inflammation, hyperresponsiveness, and remodeling. Eosinophils release toxic proteins that damage the epithelial lining and promote mucus production, leading to airflow obstruction. In addition to eosinophilic inflammation, recent studies have identified the role of innate immune responses, including epithelial cells and dendritic cells, in initiating and sustaining inflammation. In COPD, long-term exposure to environmental pollutants and smoking triggers an inflammatory response dominated by neutrophils and macrophages. These cells release proteases, such as matrix metalloproteinases (MMPs) and elastase, which degrade lung tissue and contribute to emphysema. Furthermore, oxidative stress, resulting from both external pollutants and activated immune cells, exacerbates inflammation and damages the lung tissue, leading to progressive airflow limitation and gas exchange impairment. In interstitial lung diseases (ILDs), persistent inflammation and epithelial injury lead to excessive fibroblast activation and collagen deposition, which results in pulmonary fibrosis. Key mediators such as TGF-β play a central role in promoting fibrosis by inducing the differentiation of fibroblasts into myofibroblasts, which are responsible for collagen synthesis and scar formation. Recent clinical trials have demonstrated the potential of biologics, including monoclonal antibodies targeting IL-5 and IL-13, in reducing inflammation and improving outcomes in asthma. In COPD, the development of anti-inflammatory biologics and JAK inhibitors shows promise in altering the inflammatory cascade and slowing disease progression.

Discussion

The pathophysiology of lung inflammation is complex, with different immune pathways contributing to the development and progression of respiratory diseases such as asthma, COPD, and ILDs. While these conditions share common features of chronic inflammation and tissue damage, the underlying immune mechanisms differ significantly [6]. Asthma is largely driven by Th2-mediated inflammation, with the release of cytokines such as IL-4, IL-5, and IL-13, which activate eosinophils and cause airway remodeling. COPD, on the other hand, is characterized by a neutrophil-driven inflammatory response, with oxidative stress playing a crucial role in amplifying the inflammatory response and causing airway damage. In ILDs, the persistent inflammatory process leads to fibrosis, with TGF-β playing a central role in fibroblast activation and collagen deposition. One of the major challenges in managing lung inflammation is the difficulty in targeting specific inflammatory mediators without affecting other immune processes that may be protective [7]. Corticosteroids, commonly used to control inflammation in asthma and COPD, often provide only partial relief and have significant side effects when used long-term. Furthermore, they are less effective in diseases like COPD, where the inflammation is more resistant to steroid treatment [8]. Emerging therapies, such as monoclonal antibodies targeting IL-5, IL-13, and TNF, have shown promise in reducing airway inflammation and improving clinical outcomes in asthma and COPD. Additionally, Janus kinase (JAK) inhibitors have demonstrated potential in modulating the inflammatory response in both asthma and COPD. However, these therapies are still under investigation and require further clinical validation. Personalized medicine, where treatments are tailored based on the inflammatory phenotype of the disease, is likely to improve treatment efficacy and outcomes.

Conclusion

In conclusion, lung inflammation plays a central role in the pathogenesis of chronic respiratory diseases, including asthma, COPD, and interstitial lung diseases. Each disease presents with distinct inflammatory profiles, yet all involve the activation of immune cells, release of pro-inflammatory cytokines, and tissue remodeling. The understanding of these mechanisms has paved the way for novel therapeutic approaches, particularly biologics targeting specific inflammatory mediators such as IL-5, IL-13, and TNF. These therapies have shown promise in reducing inflammation and improving clinical outcomes, particularly in asthma and COPD. Despite these advances, challenges remain in fully controlling the inflammatory processes and preventing disease progression. Current treatments such as corticosteroids and bronchodilators offer symptom relief but fail to address the underlying inflammation in many patients. As our understanding of lung inflammation deepens, new targeted therapies, including JAK inhibitors and personalized approaches based on inflammatory phenotypes, offer hope for more effective management of respiratory diseases. Continued research into the molecular mechanisms of lung inflammation will be crucial in improving therapeutic outcomes and reducing the global burden of chronic respiratory diseases.

References

1. Moon SW, Choi JS, Lee SH, Jung KS, Jung JY, et al. (2019) Thoracic skeletal muscle quantification: low muscle mass is related with worse prognosis in idiopathic pulmonary fibrosis patients. Respir Res 20: 35.

Indexed at, Google Scholar, Crossref

2. Nakano A, Ohkubo H, Taniguchi H, Kondoh Y, Matsuda T, et al. (2020) Early decrease in erector spinae muscle area and future risk of mortality in idiopathic pulmonary fibrosis. Sci Rep 10: 2312.

Indexed at, Google Scholar, Crossref

3. Tracey KJ, Wei H, Manogue KR, Fong Y, Hesse DG, et al. (1998) Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. J Exp Med 167: 1211-1227.

Indexed at, Google Scholar, Crossref

4. Durheim MT, Judy J, Bender S, Baumer D, Lucas J, et al. (2019) In-Hospital Mortality in Patients with Idiopathic Pulmonary Fibrosis: A US Cohort Study. Lung 197: 699-707.

Indexed at, Google Scholar, Crossref

5. Durheim MT, Judy J, Bender S, Neely ML, Baumer D, et al. (2020) A retrospective study of in-hospital mortality in patients with idiopathic pulmonary fibrosis between 2015 and 2018. Medicine (Baltimore) 99: 23143.

Indexed at, Google Scholar, Crossref

6. Kim HJ, Snyder LD, Adegunsoye A, Neely ML, Bender S, et al. (2021) Hospitalizations in patients with idiopathic pulmonary fibrosis. Respir Res 22: 257.

Indexed at, Google Scholar, Crossref

7. Bjoraker JA, Ryu JH, Edwin MK, Myers JL, Tazelaar HD, et al. (1998) Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 157: 199-203.

Indexed at, Google Scholar, Crossref

8. Hubbard R, Johnston I, Britton J (1998) Survival in Patients with Cryptogenic Fibrosing Alveolitis. Chest 113(2): 396-400.

Indexed at, Google Scholar, Crossref