Enhanced lung inflammatory response in whole-body compared to nose-only cigarette smoke-exposed mice

Abstract

Background Chronic obstructive pulmonary disease (COPD) is characterized by a progressive and abnormal inflammatory response in the lungs, mainly caused by cigarette smoking. Animal models exposed to cigarette smoke (CS) are used to mimic human COPD but the use of different CS protocols makes it difficult to compare the immunological and structural consequences of using a nose-only or whole-body CS exposure system. We hypothesized that when using a standardized CS exposure protocol based on particle density and CO (carbon monoxide) levels, the whole-body CS exposure system would generate a more severe inflammatory response than the nose-only system, due to possible sensitization by uptake of CS-components through the skin or via grooming. Methods In this study focusing on early COPD, mice were exposed twice daily 5 days a week to CS either with a nose-only or whole-body exposure system for 14 weeks to assess lung function, remodeling and inflammation. Results At sacrifice, serum cotinine levels were significantly higher in the whole-body (5.3 (2.3–6.9) ng/ml) compared to the nose-only ((2.0 (1.8–2.5) ng/ml) exposure system and controls (1.0 (0.9–1.0) ng/ml). Both CS exposure systems induced a similar degree of lung function impairment, while inflammation was more severe in whole body exposure system. Slightly more bronchial epithelial damage, mucus and airspace enlargement were observed with the nose-only exposure system. More lymphocytes were present in the bronchoalveolar lavage (BAL) and lymph nodes of the whole-body exposure system while enhanced IgA and IgG production was found in BAL and to a lesser extent in serum with the nose-only exposure system. Conclusion The current standardized CS-exposure protocol resulted in a higher internal load of serum cotinine in the whole-body exposure system, which was associated with more inflammation. However, both exposure systems resulted in a similar lung function impairment. Data also highlighted differences between the two models in terms of lung inflammation and remodelling, and potential sensitization to CS. Researchers should be aware of these differences when designing their future studies for an early intervention in COPD.

Clinical Factors and Quantitative CT Parameters Associated With ICU Admission in Patients of COVID-19 Pneumonia: A Multicenter Study

“…Multiple consolidations may result from the filling of alveoli by inflammatory exudation, suggesting a more severe damage of alveoli and indicating a poor outcome (35). More involvement of opacifications is supposed to be associated with the immunopathological basis that coronavirus could interact with and modify the intracellular environment during infection for the benefit of quickly replicating (36). Since a dysregulated/exuberant innate response is the dominating factor to coronavirus-mediated pathology, it was of great importance to recognize high-risk imaging features that would result in deterioration on initial admission.…”

“…We also focused on extrapulmonary abnormalities based on chest CT, finding that larger lymph nodes and coronary calcification also indicated poor outcomes, and those abnormalities could be detectable in the early stage of the disease. Enlarged lymph nodes may be resulted from severe inflammation (36). Coronary calcification may suggest the combination of CVD, which was reported as one of the most common comorbidities in critically ill patients (11).…”

Pulmonary rehabilitation restores limb muscle mitochondria and improves the intramuscular metabolic profile

“…Standard whole-body smoking exposure we used might induce more severe systemic inflammation and higher serum cotinine levels compared to nose-only exposure. [ 44 ] However, it has previously been shown that lung function and MLI reached the criteria for COPD as reported. [ 45 – 48 ] Third, we did not test the exact oxygen consumption of each animal.…”

“…Another limitation is that cigarette smoking plus nasal instillation of LPS, although used for modeling COPD for many years, [43] has been plausibly challenged. Standard whole-body smoking exposure we used might induce more severe systemic inflammation and higher serum cotinine levels compared to nose-only exposure [44] . However, it has previously been shown that lung function and MLI reached the criteria for COPD as reported [45–48] .…”

Air Pollution and the Airways: Lessons from a Century of Human Urbanization

“…It is important to take into account that several methods can be used to deliver CO in the form of cigarette smoke to the mice, namely nose-only exposure or whole-body exposure [59]. Serré et al ( 2021) compared both methods and stated that after 14 weeks of cigarette smoke exposure, the mice receiving it via whole-body exposure had more inflammation in BAL fluid while nose-only exposure led to more bronchial epithelial damage, mucus production, and airspace enlargement [60]. In contrast, Kogel et al (2021), showed also differences between nose-only exposure and whole-body exposure in ApoE -/mice (murine model for atherosclerosis) which might be specific for this mouse strain, where the nose-only mice had more lung inflammation and molecular dysregulation of the respiratory system [61].…”