Calcitonin Gene Related Peptide in Acute Exacerbation of COPD Patients Admitted to ICU

INTRODUCTION: Preliminary studies in animal models and human lung tissue from COPD patients have shown that calcitonin gene related peptide, a neuropeptide released from nerves innervating the airways and expressed in pulmonary neuro endocrine cells, has a strong broncho-stimulatory property with increased mucus secretion and induction of pro inflammatory state.(1–4) There are no studies evaluating serum levels of CGRP in acute exacerbation of COPD patients admitted to ICU(2). OBJECTIVES: To establish the role of CGRP in acute exacerbation of COPD patients admitted to ICU.(1,2) MATERIALS AND METHODS: To establish the role of CGRP in emphysema pathogenesis, serum CGRP levels were measured in 95 COPD patients admitted to ICU with acute exacerbation. CGRP levels of normal subjects without smoking history (n=30), smokers with normal lung function (n=10), stable COPD patients without exacerbation (n-21) was also measured. Additionally, we conducted animal studies and examined the effect of exogenous administration of recombinant CGRP on lung function by administering repeated intranasal doses (25 pg and 250 pg) to naïve mice over 7 consecutive days. RESULTS: Analysis revealed a significant elevation (p < 0.05) in CGRP levels in a subgroup of acute exacerbation COPD patients admitted to ICU compared to healthy individuals (Fig. 1). Additionally, CGRP levels negatively correlated with FEV1/FVC of AECOPD patients with correlation coefficient R=- 0.35 (-0.52 to -0.088) (Fig. 2). Administration of recombinant CGRP in naïve mice resulted in impaired lung function, particularly reduced lung elastance, alongside the recruitment of monocytes and macrophages. Histological examination confirmed the development of emphysematous features, with marked alveolar space enlargement. Furthermore, elastin, a key structural component of the alveolar walls, was found to be degraded following CGRP administration.(3,4) DISCUSSIONS/CONCLUSIONS: Our investigation into the involvement of calcitonin gene-related peptide (CGRP) highlights the intricate interplay between neuronal signaling and lung tissue homeostasis. The elevated CGRP levels observed in a subgroup of acute exacerbation of COPD patients, coupled with the induction of emphysema-like features in naive mice following the administration of recombinant CGRP, underscore the critical role of CGRP in mediating inflammatory responses within the lung microenvironment. GRANT ACKNOWLEDGMENT (IF ANY): Dr Sumalatha Arunachala would like to thank SERB-CII for the grant of the prime minster fellowship for PhD research.