A recent study published in the Biological & Pharmaceutical Bulletin has brought new insights into how cigarette smoke particles can lead to airway hyperreactivity (AHR), a condition associated with asthma and chronic obstructive pulmonary disease (COPD). The study, led by Min Jia and colleagues at Xi’an Medical University, explored the effect of dimethyl sulfoxide (DMSO)-extracted cigarette smoke particles (DSP) on airways using mouse models, revealing dose-dependent AHR following methacholine inhalation.
Airway hyperreactivity, or AHR, refers to a heightened response of the airways to stimuli, such as allergens, cold air, and pollutants, including cigarette smoke. This condition is characterized by the tightening of muscles around the airways, leading to symptoms that include coughing, wheezing, and shortness of breath.
In the in-vivo aspect of the study, BALB/c mice were subjected to intranasal administration of DSP at various concentrations (0.75, 1.5, or 3 µL/mL) every day for a week. Following this treatment, lung function was assessed using the flexiVent™ system. The researchers observed that the mice exhibited increased airway hyperreactivity in response to a cholinergic agent, methacholine, which was inhaled by the mice to induce airway constriction.
The in-vitro arm of the study involved exposing mouse tracheal segments to DSP to examine its direct effects on the airway. Enhanced contraction was noted in the tracheal segments in response to bradykinin, a molecule known to mediate inflammatory responses and related to AHR. Importantly, the treatment with DSP significantly increased mRNA and protein levels of bradykinin B1 and B2 receptors, which could explain the heightened contractile reaction.
Exploring further, the research team used pharmacological inhibitors to dissect the molecular pathways involved in DSP-induced AHR. The JNK (c-Jun-N-terminal kinase) mitogen-activated protein kinase pathway was pinpointed as a key player in this mechanism. Inhibition of JNK with a specific inhibitor (SP600125) was able to reduce the DSP-induced effects on the airway, suggesting that JNK is a critical mediator of the DSP response.
Additionally, the anti-inflammatory drug dexamethasone, which is often used in the treatment of AHR-related diseases, was found to attenuate the DSP-induced airway contractions, further implicating inflammation in this process.
While this study provides a controlled and mechanistic view of how cigarette smoke particles may exacerbate airway diseases, it does raise questions about the translation of these findings from mice to humans, which remains to be elucidated through clinical research.
The implications of such research are substantial given the widespread use of tobacco products worldwide, and the significant public health concerns surrounding smoking-related diseases such as COPD and asthma.
Despite the increased awareness of cigarette smoke as a major health risk, smoking remains a prevalent habit, and environmental exposure to smoke, through second-hand inhalation, continues to be problematic. Findings from such studies provide not only a better understanding of the pathophysiology of AHR but also potential therapeutic targets for intervention.
The research underscores the challenges in addressing smoking-related health issues and highlights the importance of continuing efforts to control tobacco use.
References
1. Jia M, Zhang Y, Zhang H, Qin Q, Xu CB. Cigarette Smoke Particles-Induced Airway Hyperreactivity in Vivo and in Vitro. Biol Pharm Bull. 2019;42(5):703-711. DOI:10.1248/bpb.b18-00736.
2. National Heart, Lung, and Blood Institute. What Is COPD? https://www.nhlbi.nih.gov/health/health-topics/topics/copd.
3. World Health Organization. Tobacco http://www.who.int/news-room/fact-sheets/detail/tobacco.
4. Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. 2008;8(3):183-92.
5. Jeffery PK. The development of large and small airway pathology in COPD: lessons from studies in horses. Int J Chron Obstruct Pulmon Dis. 2006;1(1):13-25.
Keywords
1. Airway Hyperreactivity Research
2. Cigarette Smoke Asthma Link
3. JNK Inhibition Airway Contraction
4. DMSO-Extracted Cigarette Smoke Particles
5. Anti-Inflammatory Treatment for AHR
The study conducted by Min Jia and colleagues is an essential addition to the literature on the health effects of cigarette smoke. It systematically delineates the role of specific molecular pathways in airway hyperreactivity induced by cigarette smoke particles and paves the way for potential therapeutic interventions. Even though the results compel further exploration in human subjects, the data offers valuable insights into how combating the inflammatory and chemical triggers of AHR can lead to better management of smoking-related respiratory ailments.