Mass spectrometry detection of inhaled drug in distal fibrotic lung

• Published in: Respiratory research 2022-05, Vol.23 (1), p.118-118, Article 118
• Main Authors: Mikolasch, Theresia A, Oballa, Eunice, Vahdati-Bolouri, Mitra, Jarvis, Emily, Cui, Yi, Cahn, Anthony, Terry, Rebecca L, Sahota, Jagdeep, Thakrar, Ricky, Marshall, Peter, Porter, Joanna C
• Format: Article
• Language: English
• Subjects: Airway management; Biopsy; Chromatography; Complications and side effects; Desorption; Diagnosis; Drug distribution; Drug dosages; Drugs; Fibrosis; Health aspects; Histopathology; Humans; Interstitial fibrosis; Ionization; Laboratory animals; Liquid chromatography; Lung - pathology; Lung diseases; Lung Diseases, Interstitial - diagnosis; Lungs; MALDI-MS imaging; Mass Spectrometry; Mass spectroscopy; Medical examination; Medical imaging; Parenchyma; Patient outcomes; Patients; Physiological aspects; Prospective Studies; Pulmonary Fibrosis - diagnostic imaging; Pulmonary Fibrosis - drug therapy; Pulmonary Fibrosis - pathology; Research ethics; Scientific imaging; Side effects; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectroscopy; Spectrum analysis; Transbronchial cryobiopsy
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-022-02026-5

Currently the only available therapies for fibrotic Interstitial Lung Disease are administered systemically, often causing significant side effects. Inhaled therapy could avoid these but to date there is no evidence that drug can be effectively delivered to distal, fibrosed lung. We set out to combine mass spectrometry and histopathology with rapid sample acquisition using transbronchial cryobiopsy to determine whether an inhaled drug can be delivered to fibrotic, distal lung parenchyma in participants with Interstitial Lung Disease. Patients with radiologically and multidisciplinary team confirmed fibrotic Interstitial Lung Disease were eligible for this study. Transbronchial cryobiopsies and endobronchial biopsies were taken from five participants, with Interstitial Lung Disease, within 70 min of administration of a single dose of nebulised ipratropium bromide. Thin tissue cryosections were analysed by Matrix Assisted Laser Desorption/Ionization-Mass Spectrometry imaging and correlated with histopathology. The remainder of the cryobiopsies were homogenised and analysed by Liquid Chromatography-tandem Mass Spectrometry. Drug was detected in proximal and distal lung samples from all participants. Fibrotic regions were identified in research samples of four of the five participants. Matrix Assisted Laser Desorption/Ionization-Mass Spectrometry imaging showed co-location of ipratropium with fibrotic regions in samples from three participants. In this proof of concept study, using mass spectrometry, we demonstrate for the first-time that an inhaled drug can deposit in distal fibrotic lung parenchyma in patients with Interstitial Lung Disease. This suggests that drugs to treat pulmonary fibrosis could potentially be administered by the inhaled route. Trial registration A prospective clinical study approved by London Camden and Kings Cross Research Ethics Committee and registered on clinicaltrials.gov (NCT03136120).