Biopsy-proved idiopathic pulmonary fibrosis: spectrum of nondiagnostic thin-section CT diagnoses.

Purpose: To document the spectrum of misleading thin-section computed tomographic (CT) diagnoses in patients with biopsy-proved idiopathic pulmonary fibrosis (IPF). Materials and Methods: This study had institutional review board approval, and patient consent was not required. Three observers, blinded to any clinical information and the purpose of the study, recorded thin-section CT differential diagnoses and assigned a percentage likelihood to each for a group of 123 patients (79 men, 44 women; age range, 27-82 years) with various chronic interstitial lung diseases, including a core group of 55 biopsy-proved cases of IPF. Patients with IPF in the core group, in whom IPF was diagnosed as low-grade probability (<30\%) by at least two observers, were considered to have atypical IPF cases, and the alternative diagnoses were analyzed further. Results: Thirty-four (62\%) of 55 biopsy-proved IPF cases were regarded as alternative diagnoses. In these atypical IPF cases, the first-choice diagnoses, expressed with high degree of probability, were nonspecific interstitial pneumonia (NSIP; 18 [53\%] of 34), chronic hypersensitivity pneumonitis (HP; four [12\%] of 34), sarcoidosis (three [9\%] of 34), and organizing pneumonia (one [3\%] of 34); in eight (23\%) of 34 cases, no single diagnosis was favored by more than one observer. Frequent differential diagnoses, although not always the first-choice diagnosis, were NSIP (n = 29), chronic HP (n = 23), and sarcoidosis (n = 9). Conclusion: In the correct clinical setting, a diagnosis of IPF is not excluded by thin-section CT appearances more suggestive of NSIP, chronic HP, or sarcoidosis. (c) RSNA, 2010

Changes in physiological, functional and structural markers of cystic fibrosis lung disease with treatment of a pulmonary exacerbation

Background: Clinical trials in cystic fibrosis (CF) have been hindered by the paucity of well characterised and clinically relevant outcome measures. Aim: To evaluate a range of conventional and novel biomarkers of CF lung disease in a multicentre setting as a contributing study in selecting outcome assays for a clinical trial of CFTR gene therapy. Methods: A multicentre observational study of adult and paediatric patients with CF (&gt;10 years) treated for a physician-defined exacerbation of CF pulmonary symptoms. Measurements were performed at commencement and immediately after a course of intravenous antibiotics. Disease activity was assessed using 46 assays across five key domains: symptoms, lung physiology, structural changes on CT, pulmonary and systemic inflammatory markers. Results: Statistically significant improvements were seen in forced expiratory volume in 1 s (p&lt;0.001, n=32), lung clearance index (p&lt;0.01, n=32), symptoms (p&lt;0.0001, n=37), CT scores for airway wall thickness (p&lt;0.01, n=31), air trapping (p&lt;0.01, n=30) and large mucus plugs (p=0.0001, n=31), serum C-reactive protein (p&lt;0.0001, n=34), serum interleukin-6 (p&lt;0.0001, n=33) and serum calprotectin (p&lt;0.0001, n=31). Discussion: We identify the key biomarkers of inflammation, imaging and physiology that alter alongside symptomatic improvement following treatment of an acute CF exacerbation. These data, in parallel with our study of biomarkers in patients with stable CF, provide important guidance in choosing optimal biomarkers for novel therapies. Further, they highlight that such acute therapy predominantly improves large airway parameters and systemic inflammation, but has less effect on airway inflammation