Periostin Levels do not Distinguish Chronic Obstructive Pulmonary Disease Patients with Frequent and Infrequent Exacerbations

Clarenbach, Christian F.; Sievi, Noriane A.; Brock, Matthias; Kohler, Malcolm; Huber, Lars C

doi:10.17140/prrmoj-3-129

Cited by 1 publication

(1 citation statement)

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“…Likewise, the role of periostin in emphysema is not yet fully understood. Notably, no correlation was found between disease progression and plasma periostin levels [ 61 ], however, plasma periostin was found to significantly correlate with the improved lung function (measured by FEV1) of emphysema patients undergoing treatment of inhaled corticosteroids and long-acting beta antagonists [ 62 ]. The link between the proteins upregulated by 2FN or 3FN and emphysema remains unclear, therefore, further exploration of 2FN and 3FN efficacy is necessary to determine the future potential of the formulations as a treatment for emphysema.…”

Section: Discussionmentioning

confidence: 99%

Development of Inhalable Spray Dried Nitrofurantoin Formulations for the Treatment of Emphysema

et al. 2022

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A central characteristic of emphysematous progression is the continuous destruction of the lung extracellular matrix (ECM). Current treatments for emphysema have only addressed symptoms rather than preventing or reversing the loss of lung ECM. Nitrofurantoin (NF) is an antibiotic that has the potential to induce lung fibrosis as a side effect upon oral administration. Our study aims to repurpose NF as an inhalable therapeutic strategy to upregulate ECM expression, thereby reversing the disease progression within the emphysematous lung. Spray-dried (SD) formulations of NF were prepared in conjunction with a two-fluid nozzle (2FN) and three-fluid nozzle (3FN) using hydroxypropyl methylcellulose (HPMC) and NF at 1:1 w/w. The formulations were characterized for their physicochemical properties (particle size, morphology, solid-state characteristics, aerodynamic behaviour, and dissolution properties) and characterized in vitro with efficacy studies on human lung fibroblasts. The 2FN formulation displayed a mass mean aerodynamic diameter (MMAD) of 1.8 ± 0.05 µm and fine particle fraction (FPF) of 87.4 ± 2.8% with significantly greater deposition predicted in the lower lung region compared to the 3FN formulation (MMAD: 4.4 ± 0.4 µm; FPF: 40 ± 5.8%). Furthermore, drug dissolution studies showed that NF released from the 2FN formulation after 3 h was significantly higher (55.7%) as compared to the 3FN formulation (42.4%). Importantly, efficacy studies in human lung fibroblasts showed that the 2FN formulation induced significantly enhanced ECM protein expression levels of periostin and Type IV Collagen (203.2% and 84.2% increase, respectively) compared to untreated cells, while 3FN formulations induced only a 172.5% increase in periostin and a 38.1% increase in type IV collagen. In conclusion, our study highlights the influence of nozzle choice in inhalable spray-dried formulations and supports the feasibility of using SD NF prepared using 2FN as a potential inhalable therapeutic agent to upregulate ECM protein production.

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Section: Discussionmentioning

confidence: 99%