INTRODUCTION:Mediastinal granuloma (MG) is a postinfectious complication of histoplasmosis that remains a rare diagnosis in the pediatric literature. This case series presents a well phenotyped population to further characterize this disease process. METHODS:Thirty cases of MG in children under 21 years-of-age presenting over a 16-year period were retrospectively analyzed. RESULTS:Seventy-five percent of patients presented with respiratory symptoms. Histoplasma antigen was negative in 90%. Histoplasma antibody was positive in 100%. Fine needle aspirates were positive for histoplasma in 31% whereas excisional biopsy was positive in 71%. Bronchoalveolar lavage (BAL) was negative for histoplasma in all cases where performed. Computed tomography revealed 53% of MGs were right paratracheal, 60% had internal calcifications, and 23% had splenic calcifications. Sixteen patients (53%) were managed with medical therapies only, with 7 (44%) treated with steroids and antifungals and 7 (44%) with antifungals alone. The remaining 14 patients (47%) underwent surgical excision and 9 were also treated with antifungals (64%). Bronchial compression was the most common comorbidity within the medically managed only group whereas vascular compression and fistulation were most common within the surgically managed group. CONCLUSION:Respiratory symptoms should raise suspicion for MG. Diagnostic evidence of MG includes positive histoplasma serologies, right paratracheal location, internal calcifications, and splenic calcifications. Bronchoscopy, BAL and needle biopsies provide minimal diagnostic benefit. Antifungals are used in the majority of cases, whereas steroids are used most often in non-surgically managed patients with airway compression. Indications for surgical resection are less defined, but include vascular compression and fistulation unresponsive to medical treatment.

Rationale: We investigated the relationship between self-reported environmental exposures, disease outcomes and radiologic findings in individuals with familial pulmonary fibrosis (FPF).Methods: This prospective cohort study includes adults with FPF who had self-reported environmental exposures at the time of study enrollment using a standardized questionnaire.Individual exposures were grouped based on biologic similarity and mode of exposure: inorganic dusts, organic dusts, gases/fumes, metals, chemicals, elements.Disease outcomes of interest include age at symptom onset and age at lung transplantation or death, captured via chart review.Cox proportional hazard models test the association between exposure groups and outcomes.Kaplan-Meier plots display survival probability according to exposure status.In a subset of subjects with archived chest computed tomography (CT) images, a thoracic radiologist blinded to clinical history documented specific findings utilizing a standardized form.The proportion of subjects with a given exposure was compared between subjects with hypersensitivity pneumonitis (HP)-associated features on chest CT (defined as any ground glass, mosaic attenuation, air trapping, centrilobular nodules, diffuse or upper lung craniocaudal disease distribution, or diffuse or central lung axial distribution) and those without these features.Results: Subjects (n=279) included 173 (62.0%) males and 164 (58.8%) ever-smokers with mean percent predicted FVC (n=211) of 68.5 (SD 18.9) and DLCO (n=197) of 54.8 (SD 21.9).The median age at symptom onset was 64.0 years (95% CI 62.0-65.0)and median age at transplant or death was 71.2 years (95% CI 69.3-73.4);216 (77.4%) individuals experienced transplant (n=36) or death.One hundred and forty five (52.0 %) subjects reported exposure to organic dusts, 134 (48.0%) to inorganic dusts, 125 (44.8%) to chemicals, 88 (31.5%) to gases/fumes, 65 (23.3%) to metals, and 24 (8.6%) to elements.Organic dust exposure was associated with earlier age at symptom onset (HR 1.34, 95% CI 1.05-1.70;p=0.02) but not an earlier age at death (HR 1.18, 95% CI 0.89-1.54;p=0.24) (Figure).Other exposure groups were not associated with a statisticallysignificant difference in age at symptom onset or death.Among 159 subjects with a chest CT and exposure questionnaire, a larger proportion of subjects with HP-associated CT features reported organic dust exposure (37/54, 68.5%) compared to those without these CT features (55/105, 52.4%), chi-squared p=0.05.Conclusions: Exposure to organic dust is common and appears to influence radiologic and clinical manifestations of FPF, including modestly earlier symptom onset, thereby suggesting an interaction between environmental and genetic risk factors in susceptible individuals.

Extracorporeal photopheresis (ECP) is a treatment used for chronic lung allograft dysfunction (CLAD). The optimal number of ECP treatments is unknown. Furthermore, the trajectory of lung function decline and patient survival after cessation of ECP is not well described.