Pulmonary epithelial markers in phenotypes of chronic lung allograft dysfunction.

BACKGROUND: Airway epithelial injury is thought to be a key event in the pathogenesis of chronic lung allograft dysfunction (CLAD). We investigated whether markers of epithelial activity and injury in bronchoalveolar lavage fluid (BAL) correlate with CLAD diagnosis and major CLAD phenotypes: bronchiolitis obliterans syndrome (BOS) vs restrictive allograft syndrome (RAS)-related phenotypes (including RAS, mixed phenotype, and all other patients with RAS-like opacities). METHODS: CLAD status and phenotypes were retrospectively determined in a cohort of all consecutive adult, first, bilateral lung transplants performed 2010-2015, with available BAL samples. All patients with RAS-related phenotypes were included and 1:1 matched with BOS patients based on the time from transplant to CLAD-onset. Subjects who were CLAD-free for a minimum of 3 years post-transplant were 1:1 matched to CLAD patients and included as controls. Proteins that maintain the barrier function of the airway epithelial mucosa (club cell secretory protein, surfactant protein-D and epithelial mucins: MUC1, MUC5AC, MUC5B, MUC16), as well as epithelial cell death markers (M30&M65 representing epithelial cell apoptosis and overall death, respectively), were measured in BAL obtained within 6-months post CLAD onset using a double-sandwich ELISA or a multiplex bead assay. Protein levels were compared using Mann-Whitney-U-test. Association between protein levels and graft survival was assessed using Cox proportional hazards models, adjusted for CMV serology mismatch status and CLAD phenotype. RESULTS: Fifty-four CLAD (27 BOS, 11 RAS, 7 mixed, 9 others with RAS-like opacities) patients and 23 CLAD-free controls were included. Median BAL levels were significantly higher in patients with CLAD compared to CLAD-free controls for M30 (124.5 vs 88.7 U/L), MUC1 (6.8 vs 3.2 pg/mL), and MUC16 (121.0 vs 30.1 pg/mL). When comparing CLAD phenotypes, M30 was significantly higher in patients with RAS-related phenotypes than BOS (160.9 vs 114.6 U/L). In multivariable models, higher M30 and MUC5B levels were associated with decreased allograft survival after CLAD onset independent of phenotype (p < 0.05 for all). CONCLUSIONS: Airway epithelial mucins and cell death markers are enhanced in the BAL of patients with CLAD and can assist in differentiating between CLAD phenotypes and post-CLAD outcomes. Abnormal airway mucin expression and epithelial cell death may be involved in the pathogenesis of CLAD, and therefore their detection may aid in future selection of targeted therapies.

Do we need biomarkers for the follow-up and shortening of antibiotic treatment duration?

PURPOSE OF REVIEW: Clinical and laboratory parameters are useful tools for the diagnosis, follow-up and evaluation of resolution, and to predict outcomes when measured at different time-points onset and serially during follow-up in patients with hospital-acquired pneumonia and/or ventilator-associated pneumonia (HAP/VAP). RECENT FINDINGS: Both, the 2017 ERS/ESICM/ESCMID/Asociación Latino Americana de Tórax (EEEAG) and the 2016 IDSA/ATS guidelines (IAG) for the management of HAP/VAP recommend using clinical criteria alone, rather than biomarkers for diagnosis. Several studies were conducted to assess the value of serum biomarker concentration and kinetics for predicting the outcome in HAP/VAP, including C-reactive protein and procalcitonin (PCT). Although the EEEAG do not recommend routinely performing biomarker determinations in addition to bedside clinical assessment in patients receiving antibiotic treatment for VAP or HAP to predict adverse outcomes and clinical response, the IAG recommend that routine bedside clinical assessment should be accompanied by measurements of PCT to guide antimicrobial therapy. Additionally, the 2016 Surviving Sepsis Campaign also suggests that PCT levels can be used to support the shortening of antibiotic therapy. SUMMARY: Current evidence indicate that there is no recommendation to use biomarkers systematically to guide every decision. However, in some circumstances they might add some relevant information to our everyday practice.

[Hypersensitivity pneumonitis. A series of nine cases with surgical lung biopsy]. / Neumonitis por hipersensibilidad. Serie de nueve casos con biopsia pulmonar quirúrgica.

In a series of nine patients with histopathological diagnosis of hypersensitivity pneumonitis, we retrospectively evaluated clinical data, exposure related factors, pulmonary function tests and chest computed tomography scans. A restrictive abnormality with reduction of diffusion capacity for carbon monoxide was mainly found. Chest scans showed fibrotic patterns in most cases; ground glass attenuation areas with mosaic pattern and consolidation in the rest. Exposure to avian antigens, cereal grains and air conditioners contaminated with fungi yeasts and bacteria, were suspected from clinical data in two-thirds of the cases. Since there are no unique features that allow differentiation from other interstitial lung diseases, a high clinical suspicion is required and a careful search of environmental exposure to possible antigens is needed that, together with clinical, radiological and pathological data, may lead to diagnosis.

Neumonitis por hipersensibilidad: Serie de nueve casos con biopsia pulmonar quirúrgica / Hypersensitivity pneumonitis. A series of nine cases with surgical lung biopsy

En una serie de nueve pacientes con diagnóstico histopatológico de neumonitis por hipersensibilidad, se revisaron en forma retrospectiva la historia clínica, los factores de exposición, las pruebas de función pulmonar y las tomografías computarizadas de tórax. La función pulmonar evidenció principalmente compromiso restrictivo con disminución de la difusión de monóxido de carbono. Las tomografías de tórax mostraron patrones fibróticos en la mayoría de los casos; áreas de vidrio esmerilado con patrón en mosaico y áreas de consolidación en el resto. Pudo detectarse exposición a antígenos aviarios, granos de cereales y acondicionadores de aire contaminados con esporas de hongos y bacterias, en dos tercios de los casos. Dado que no existen características únicas que permitan diferenciar la neumonitis por hipersensibilidad de otras enfermedades del intersticio pulmonar, se requiere de un alto índice de sospecha clínica y de una detallada búsqueda de exposición ambiental que deberán complementarse con los datos clínicos, radiológicos y de anatomía patológica para llegar al diagnóstico.

In a series of nine patients with histopathological diagnosis of hypersensitivity pneumonitis, we retrospectively evaluated clinical data, exposure related factors, pulmonary function tests and chest computed tomography scans. A restrictive abnormality with reduction of diffusion capacity for carbon monoxide was mainly found. Chest scans showed fibrotic patterns in most cases; ground glass attenuation areas with mosaic pattern and consolidation in the rest. Exposure to avian antigens, cereal grains and air conditioners contaminated with fungi yeasts and bacteria, were suspected from clinical data in two-thirds of the cases. Since there are no unique features that allow differentiation from other interstitial lung diseases, a high clinical suspicion is required and a careful search of environmental exposure to possible antigens is needed that, together with clinical, radiological and pathological data, may lead to diagnosis.