Kramer, EL; Hardie, WD; Madala, SK; Davidson, C; Clancy, JP. Subacute TGF beta expression drives inflammation, goblet cell hyperplasia, and pulmonary function abnormalities in mice with effects dependent on CFTR function. American journal of physiology. Lung cellular and molecular physiology. 2018; 315(3):L456-L465.
Cystic fibrosis (CF) causes a highly variable lung disease; although TGFbeta is a well-known genetic modifier of this disease, its mechanism of action in CF is unknown. In this study, subacute pulmonary TGFbeta exposure was demonstrated to induce CF relevant lung disease, including goblet cell hyperplasia and inflammation, in a CF mouse model. CF mice exposed to TGFbeta had worse lung function and airway hyperreactivity than non-CF mice, indicating TGFbeta may be an important therapeutic target in CF.
Walkup, LL; Towe, CT; Bdaiwi, A; Merrow, AC; Hammill, AM; Cleveland, ZI; Woods, JC. Evidence of Normal Alveolar Size in Pediatric Generalized Lymphatic Anomaly. American journal of respiratory and critical care medicine. 2018; 198(12):1573-1574.
In a rare case of generalized lymphatic anomaly, hyperpolarized 129Xe gas MRI suggested uniform lung ventilation and normal alveolar size despite long-term pleural effusions that likely reduced the overall lung volume. In the future, 129Xe MRI may be helpful for individualizing therapies with longitudinal, quantitative regional assessment and for investigating the pathophysiological mechanisms of rare-lung diseases and disorders.
Sontake, V; Kasam, RK; Sinner, D; Korfhagen, TR; Reddy, GB; White, ES; Jegga, AG; Madala, SK. Wilms tumor 1 drives fibroproliferation and myofibroblast transformation in severe fibrotic lung disease. JCI insight. 2018; 3(16).
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease that is incurable, and nearly 130,000 Americans suffer, with an estimated 50,000 new cases diagnosed each year. Although it is well accepted that myofibroblast accumulation is a central component of pathogenesis in IPF, the transcriptional program(s) that orchestrate myofibroblast transformation are poorly defined. In this paper, we demonstrate for the first time that Wilms’ Tumor 1 (WT1) functions as a positive regulator of fibroproliferation and myofibroblast transformation. Our findings indicate a new phenomenon called mesothelial-to-myofibroblast transformation during subpleural thickening and fibrosis in IPF.
Guilbert, TW; Bacharier, LB; Mauger, DT; Phipatanakul, W; Szefler, SJ; Boehmer, S; Beigelman, A; Fitzpatrick, AM; Jackson, DJ; Baxi, SN; Benson, M; Burnham, CD; Cabana, MD; Castro, M; Chmiel, JF; Covar, R; Daines, M; Gaffin, JM; Gentile, DA; Holguin, F; Israel, E; Kelly, HW; Lazarus, SC; Jr, LR F; Ly, N; Meade, K; Morgan, W; Moy, J; Olin, JT; Peters, SP; Pongracic, JA; Raissy, HH; Ross, K; Sheehan, WJ; Sorkness, C; Teague, WG; Thyne, S; Martinez, FD; National Heart, Lung, and Blood Institute's AsthmaNet. Challenges in assessing the efficacy of systemic corticosteroids for severe wheezing episodes in preschool children. Journal of Allergy and Clinical Immunology. 2019; 143(5):1934-1937.e4.
This study assessed the efficacy of oral corticosteroids (OCS) in preschool-aged children with recurrent severe wheezing. The trial was prematurely terminated by the Data Safety and Monitoring Board given the high rate of protocol noncompliance (open label OCS use). It was observed that most children experienced a short duration of symptoms with only mild lower respiratory tract symptoms at 36-72 hours of illness. It may be helpful to conduct future studies in a clinical rather than home setting to confirm that protocol-defined criteria for OCS intervention are met and to compare OCS to another active therapy such as azithromycin rather than placebo. 
He, Z; Armoni Domany, K; Nava-Guerra, L; Khoo, MC K; DiFrancesco, M; Xu, Y; McConnell, K; Hossain, MM; Amin, R. Phenotype of Ventilatory Control in Children With Moderate to Severe Persistent Asthma and Obstructive Sleep Apnea.. Sleep. 2019.
We describe for the first time in children with moderate to severe persistent asthma a phenotype of children with severely abnormal lung function based on parameters that describe ventilatory control. Subjects with severely abnormal lung function have 2 essentials characteristics, elevated plant gain and decreased chemoreceptor sensitivity. The clinical significance of this observation is demonstrated by the association between plant gain and the severity of OSA and the severity of airway obstruction, such that plant gain increases with increasing OI and an increase in airway obstruction measured by FEV1 and FEV1/FVC. Our results demonstrate that OSA in children with moderate to severe persistent asthma is associated with a diminished capacity of the lungs to maintain blood gas homeostasis as measured by plant gain.