The Novel CFTR Mutation A457P in a Male with a Delayed Diagnosis of Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive disease that may be caused by more than 1000 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We describe the case of a CF patient who was initially diagnosed at 16 years of age after presenting with mild respiratory compromise and pancreatic sufficiency. When genetic testing was first performed using a CF mutation panel, only a single F508del CFTR allele was identified. We subsequently performed testing, which revealed a previously unreported mutation: A457P (p.Ala457Pro, c.1369G>C). The patient's clinical course through adulthood is described, and genotype-phenotype correlation is discussed. The A457P mutation appears to confer a relatively mild phenotype, as is usually observed with CFTR class IV–VI defects. With the advent of more comprehensive and widely available genetic testing techniques, identification of CF genotypes in patients with milder disease variants may help stratify patients for targeted therapy and prevent late complications of the disease

Electromagnetic navigation transthoracic needle aspiration for the diagnosis of pulmonary nodules: A safety and feasibility pilot study

BACKGROUND: Pulmonary nodules remain a diagnostic challenge for physicians. Minimally invasive biopsy methods include bronchoscopy and CT guided transthoracic needle aspiration (TTNA). A novel electromagnetic guidance transthoracic needle aspiration (ETTNA) procedure which can be combined with navigational bronchoscopy (NB) and endobronchial ultrasound (EBUS) in a single setting has become available. METHODS: A prospective pilot study examining the safety, feasibility and diagnostic yield of ETTNA in a single procedural setting. All patients enrolled underwent EBUS for lung cancer staging followed by NB and ETTNA. Feasibility of performing ETTNA and a safety assessment by recording procedural related complications including pneumothorax or bleeding was performed. Diagnostic yield of ETTNA defined by a definitive pathologic tissue diagnosis was recorded. An additional diagnostic yield analysis was performed using a cohort analysis of combined interventions (EBUS + NB + ETTNA). All non-diagnostic biopsies were either followed with radiographic imaging or a surgical biopsy was performed. RESULTS: Twenty-four subjects were enrolled. ETTNA was feasible in 96% of cases. No bleeding events occurred. There were five pneumothoraces (21%) of which only two (8%) subjects required drainage. The diagnostic yield for ETTNA alone was 83% and increased to 87% (P=0.0016) when ETTNA was combined with NB. When ETTNA and NB were performed with EBUS for complete staging, the diagnostic yield increased further to 92% (P=0.0001). CONCLUSIONS: This is the first human pilot study demonstrating an acceptable safety and feasibility profile with a novel ETTNA system. Further studies are needed to investigate the increased diagnostic yield from this pilot study

Chronic immune checkpoint inhibitor pneumonitis

Background Pneumonitis from immune checkpoint inhibitors (ICI) is a potentially fatal immune-related adverse event (irAE) from antiprogrammed death 1/programmed death ligand 1 immunotherapy. Most cases of ICI pneumonitis improve or resolve with 4–6 weeks of corticosteroid therapy. Herein, we report the incidence, clinicopathological features and management of patients with non-small cell lung cancer (NSCLC) and melanoma who developed chronic ICI pneumonitis that warrants ≥12 weeks of immunosuppression.Methods Patients with ICI pneumonitis were identified from institutional databases of ICI-treated patients with advanced melanoma and NSCLC between January 2011 and July 2018. ICI pneumonitis was defined as clinical/radiographic evidence of lung inflammation without alternative diagnoses, adjudicated by a multidisciplinary team. Chronic ICI pneumonitis was defined as pneumonitis that persists or worsens with steroid tapering, and necessitates ≥12 weeks of immunosuppression, after ICI discontinuation. Serial chest CT was used to assess radiological features, and tumor response by Response EvaluationCriteria for Solid Tumors V.1.1. Bronchoalveolar lavage fluid (BALF) samples were assessed by cell differential. Lung biopsy samples were evaluated by H&E staining and multiplex immunofluorescence (mIF), where available.Results Among 299 patients, 44 developed ICI pneumonitis (NSCLC: 5/205; melanoma: 1/94), and of these, 6 experienced chronic ICI pneumonitis. The overall incidence of chronic ICI pneumonitis was thus 2%. Of those who developed chronic ICI pneumonitis: the majority had NSCLC (5/6), all sustained disease control from ICIs, and none had other concurrent irAEs. Timing of chronic ICI pneumonitis development was variable (range: 0–50 months), and occurred at a median of 12 months post ICI start. Recrudescence of ICI pneumonitis occurred at a median of 6 weeks after initial steroid start (range: 3–12 weeks), with all patients requiring steroid reintroduction when tapered to ≤10 mg prednisone/equivalent. The median total duration of steroids was 37 weeks (range: 16–43+weeks). Re-emergence of radiographic ICI pneumonitis occurred in the same locations on chest CT, in most cases (5/6). All patients who developed chronic ICI pneumonitis had BALF lymphocytosis on cell differential and organising pneumonia on lung biopsy at initial ICI pneumonitis presentation, with persistent BALF lymphocytosis and brisk CD8+ infiltration on mIF at pneumonitis re-emergence during steroid taper.Conclusions A subset of patients who develop pneumonitis from ICIs will develop chronic ICI pneumonitis, that warrants long-term immunosuppression of ≥12 weeks, and has distinct clinicopathological features

Computed Tomography during Bronchoscopic Lung Splinting for Atelectasis

A 64-year-old man experienced persistent atelectasis of the right lung following right upper lobectomy. To simultaneously visualize the airways and lung parenchyma in real-time, chest computed tomography was performed while pneumatically splinting the lung open via insufflation through the working channel of a bronchoscope. The bronchi were patent but peripheral consolidations within the remaining right lung were visualized, representative of pneumonia. The patient fully recovered with antimicrobial therapy. CT during bronchoscopic pneumatic lung splinting is an advanced diagnostic for the investigation of persistent atelectasis