Singh, A

Abstract Rationale The diagnosis of interstitial lung disease (ILD) requires a multidisciplinary discussion (MDD), in which high-resolution computed tomography (HRCT) and histopathology play key roles. Genomic classifiers have recently been introduced for clinical use, in which lung tissue obtained via transbronchial forceps biopsy undergoes whole-transcriptome RNA sequencing followed by gene expression analysis. These molecular tools are particularly valuable in establishing a diagnosis of idiopathic pulmonary fibrosis (IPF) in patients without a definite usual interstitial pneumonia (UIP) pattern on imaging. Although genomic classifiers are increasingly utilized in clinical practice, data on their diagnostic performance continue to evolve, warranting an updated analysis of the current evidence. Methods A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Comprehensive search of PubMed, MEDLINE, Embase, Scopus and the Cochrane Library were performed through October 2025 using predefined terms including “genomic classifier,” “Envisia,” “UIP,” and “interstitial lung disease.” Eligible studies were which enrolled adult patients with ILD of uncertain etiology in whom genomic classifiers were compared with histopathologic or MDD based reference standards. True positive, false positive, false negative, and true negative data were extracted to calculate pooled estimates of sensitivity, specificity and the area under the receiver-operating characteristic curve (AUROC) using a random-effects bivariate model. Results Six studies comprising 347 patients met inclusion criteria, with sample sizes ranging from 24 to 98 participants. Across studies, sensitivity ranged from 59% to 85% and specificity from 75% to 100%. The pooled sensitivity was 68% (95% CI, 60-76%; P < 0.001) and specificity 77% (95% CI, 70-85%; P < 0.001), with an estimated AUROC of 0.73 (95% CI, 0.65-0.81) indicating discriminative performance. In two studies evaluating clinical impact, incorporation of genomic classifier data into MDD increased diagnostic confidence in ILD subtyping by 30-50%. No major adverse events related to transbronchial tissue acquisition were reported. Conclusions Genomic classifiers represent a promising, less invasive adjunct for identifying UIP patterns in ILD, demonstrating good overall diagnostic accuracy. Incorporating classifier results within MDD frameworks enhances diagnostic confidence and may reduce the need for surgical lung biopsy in appropriately selected patients. However, small study sizes, potential funding bias and limited accessibility highlight the need for larger, independently conducted prospective studies to further define their role in future IPF diagnostic algorithms. This abstract is funded by: None

Abstract Introduction Aminoglycoside antibiotics are well known to cause cochlear and vestibular toxicity when used systemically. Inhaled tobramycin was developed to reduce systemic exposure and is considered safer with only rare reports of ototoxicity have been reported in patients with renal dysfunction. We describe a case of bilateral sensorineural hearing loss (SNHL) and tinnitus associated with inhaled tobramycin in a patient without renal impairment, emphasizing that even inhaled formulations can induce significant auditory toxicity in susceptible individuals. Case A 85 year old woman with Sjogren’s related interstitial lung disease and bronchiectasis who was chronically colonized by Pseudomonas aeruginosa was treated with inhaled tobramycin for recurrent infections. She had normal renal function and no prior aminoglycoside exposure. After approximately three months of inhaled therapy, she noted progressive bilateral hearing decline and high pitched tinnitus without vertigo or otalgia. Physical examination revealed clear ear canals and intact tympanic membranes. Baseline audiometry one year ago had demonstrated mild to moderately-severe bilateral SNHL. Repeat testing after tobramycin exposure showed worsening thresholds and reduced word recognition bilaterally. MRI of the brain and internal auditory canals was unremarkable. Serum creatinine remained normal throughout treatment. Inhaled tobramycin was discontinued, after which hearing loss stabilized. No further progression was observed on follow-up audiometry. Discussion Although systemic absorption from inhaled tobramycin is typically low, elderly and low-body-weight patients may accumulate sufficient serum levels to cause cochlear injury. Mechanisms include reactive oxygen species mediated hair cell toxicity and possible genetic susceptibility involving the mitochondrial 12S rRNA mutation. Prior reports of vestibulotoxicity and cochleotoxicity from inhaled tobramycin primarily involved patients with renal dysfunction, however, this case report demonstrates that toxicity can occur despite preserved renal function. Clinicians should maintain vigilance for otologic symptoms in patients receiving inhaled aminoglycosides. Baseline and periodic audiometric monitoring should be incorporated into chronic treatment protocols. This abstract is funded by: None