Predictive factors for dose reduction and discontinuation of nintedanib in fibrotic interstitial lung diseases: Real life data.

Nintedanib, an intracellular inhibitor targeting multiple tyrosine kinases, has emerged as a standard treatment for various fibrotic lung diseases. Despite its efficacy, side effects such as nausea, diarrhea, and hepatotoxicity often lead to dose reduction or discontinuation. In this retrospective analysis at an university hospital's interstitial lung disease clinic, we aimed to identify baseline characteristics associated with dose adjustment or treatment discontinuation. Of the 58 patients included, 41.4% maintained the full nintedanib dose, while 31.0% required dosage reduction, and 27.6% discontinued treatment due to adverse events, predominantly gastrointestinal and hepatotoxic effects. Multivariate analysis revealed body surface area (BSA) as an independent and significant baseline risk factor (adjusted Odds Ratio [aOR] 0.22), suggesting a 78% decreased chance of requiring dose modification for every decimal point increase in BSA. A BSA cutoff of ≤1.73 m [2] exhibited a sensitivity of 73% and specificity of 91.7%, with significant impact on one-year survival under full-dose treatment (p < 0.001). Lower BSA was associated with early onset adverse effects, particularly gastrointestinal, supporting the need for regular clinical monitoring. The study emphasizes the importance of recognizing baseline factors to ensure the safety and tolerability of nintedanib, thereby preventing the progression of pulmonary fibrosis. These findings contribute to the evolving understanding of nintedanib management in fibrotic interstitial lung diseases, guiding clinicians in personalized treatment approaches.

NK and NKT cells in the diagnosis of diffuse lung diseases presenting with a lymphocytic alveolitis.

BACKGROUND: Diffuse lung diseases (DLD) are characterized by different immunophenotypes in the bronchoalveolar lavage fluid (BALF). We aimed to evaluate the diagnostic value of BALF NK and NKT cell counts of patients with DLD and lymphocytic alveolitis. METHODS: We assessed 202 patients with DLD, who underwent BALF immunophenotyping. Samples were routinely processed by flow cytometry and lymphocyte subsets were compared between patients with sarcoidosis (n = 106), hypersensitivity pneumonitis (HP; n = 53), and other DLDs (n = 43). We compared absolute counts and percentages of NK and NKT cells between patients with HP versus the remaining DLD patients. To assess the accuracy of BALF lymphocyte subsets in the diagnosis of HP, we calculated the respective areas under the receiver operating characteristic curves (AUC-ROC). RESULTS: Patients with HP had significantly higher numbers of BALF NK cells, and its percentage was significantly associated with a higher odds of HP, even after adjustment for the NKT and CD8+ cells. For the absolute number of BALF NK cells, we found an AUC-ROC of 0.76 (95%CI = 0.68-0.84) when comparing patients with HP versus the remaining DLD. The cut-offs of 2000 NK cells/mL and of 2.4% NK cells in the BALF had a specificity and a negative predictive value over 80% for the diagnosis of HP. BALF NK cells absolute counts were significantly higher in HP patients with a restrictive pattern. No such differences were observed for NKT cells. CONCLUSIONS: BALF NK immunophenotyping may be a helpful adjunct to the diagnostic work-up of DLD, particularly in the differential diagnosis of HP.

Diagnostic Yield of Computed Tomography-Guided Transthoracic Lung Biopsy in Diffuse Lung Diseases.

BACKGROUND: Accurate diagnosis is essential for successful management of diffuse lung disease (DLD). Histopathology may sometimes be necessary. Surgical lung biopsy, the gold standard, carries a risk of morbidity and mortality. Computed tomography (CT) guided transthoracic lung biopsy (CT-TLB) is a minimally invasive method for obtaining lung tissue. However, its diagnostic yield is unknown in DLD. OBJECTIVE: To assess the diagnostic yield of CT-TLB in DLD according to the predominant high-resolution CT (HRCT) patterns. METHODS: Between January 2009 and December 2016, we enrolled all consecutive adult patients with suspicion of DLD who underwent CT-guided transthoracic lung biopsy during the diagnostic work-up. All biopsies were performed by a senior interventional radiologist using CT fluoroscopy. RESULTS: The study included 169 patients (50.3% men) with a mean (±SD) age of 58.3 ± 14 years. Consolidation was the predominant HRCT pattern. A definitive or probable diagnosis was made in 66.3%. The most frequent diagnosis was organizing pneumonia (36.2%). Diagnostic yield was higher when the predominant HRCT pattern was consolidation or nodular. The most common complication was pneumothorax (17.8%); other complications included mild hemoptysis (7.7%), hemothorax (1.2%), and death (0.59%). No acute exacerbation of the underlying condition was observed. CONCLUSIONS: CT-TLB proved to be accurate and safe for the diagnosis of DLD. The overall diagnostic yield of the procedure was 66.3%. Given its low complication rates, CT-TLB can be an option in patients whose respiratory function is seriously impaired and in those with substantial comorbidities, where more invasive procedures cannot be performed for reasons of safety.

Pulmonary inflammatory myofibroblastic tumor: report of 2 cases with radiologic-pathologic correlation.

Inflammatory myofibroblastic tumor is a rare benign tumor that affects most commonly children and young adults. In the lung, it comprises less than 1% of all neoplasms. The authors describe the clinical, radiological, and pathologic features of 2 cases of incidentally discovered pulmonary inflammatory myofibroblastic tumors.

Acute fibrinous and organizing pneumonia: A report of 13 cases in a tertiary university hospital.

INTRODUCTION: Acute fibrinous and organizing pneumonia (AFOP) is a rare diffuse pulmonary disease, but it is not yet known whether it is a distinct form of interstitial pneumonia or simply a reflection of a tissue sampling issue. METHODS: Cross-sectional evaluation of clinical and radiological findings, treatments, and outcomes for patients with histologically confirmed AFOP at a tertiary university hospital between 2002 and 2015. RESULTS: Thirteen patients (7 women, 53.8%) with a mean ±â€ŠSD age of 53.5 ±â€Š16.1 years were included. The main symptoms were fever (69.2%), cough (46.2%), and chest pain (30.8%). All patients presented a radiological pattern of consolidation and 5 (38.5%) had simultaneous ground-glass areas. Histology was obtained by computed tomography-guided transthoracic biopsy in 61.5% of cases and by surgical lung biopsy in the remaining cases. Several potential etiologic factors were identified. Eight patients (61.5%) had hematologic disorders and 3 had undergone an autologous hematopoietic cell transplant. Two (15.4%) had microbiologic isolates, 5 (38.4%) had drug-induced lung toxicity, and 2 (15.4%) were classified as having idiopathic AFOP. In addition to antibiotics and diuretics used to treat the underlying disease, the main treatment was corticosteroids, combined in some cases with immunosuppressants. Median survival was 78 months and 6 patients (46.2%) were still alive at the time of analysis. CONCLUSION: Our findings for this series of patients confirm that AFOP is a nonspecific reaction to various agents with a heterogeneous clinical presentation and clinical course that seems to be influenced mainly by the severity of the underlying disorder.