Neumatocele en paciente pediátrico. ¿Cuándo debemos actuar? / Pneumatocele in a pediatric patient. When should we act?

El neumatocele es una lesión cavitada llena de aire de carácter adquirido que se encuentra en el interior del parénquima pulmonar. Aunque las causas pueden variar, el origen infeccioso bacteriano es lo más frecuente. Los cambios en los serotipos de neumococo y el aumento de las neumonías necrotizantes observado en las últimas décadas hacen de este tipo de lesiones algo cada vez más frecuente. Es importante conocer la evolución esperable, así como también saber qué paciente se beneficia de intervención para evitar secuelas a largo plazo y complicaciones graves. En este artículo se exponen las causas, epidemiología, orientación diagnóstica y una propuesta de manejo para el neumatocele.

A pneumatocele is an air-filled cavitary lesion of acquired nature located within the pulmonary parenchyma. Although causes can vary, bacterial infectious origin is the most common. Changes in pneumococcal serotypes and the increase in necrotizing pneumonia observed in recent decades have made these lesions increasingly frequent. It is important to know the expected evolution and to identify which patients would benefit from intervention to prevent long-term sequelae and severe complications. This article exposes the causes, epidemiology, diagnostic approach, and a management proposal for pneumatocele.

Canine Visceral Leishmaniasis: A Histological and Immunohistochemical Study of Fibropoiesis in Chronic Interstitial Pneumonitis.

We studied some fibrotic aspects of chronic interstitial pneumonitis in the lungs of dogs infected with Leishmania infantum. The lungs of eleven naturally infected dogs, twelve experimentally infected with two distinct strains of L. infantum (BH401 and BH46), and six uninfected (controls) dogs, were analyzed by histological, parasitological, and immunohistochemical studies. Conventional histology (HE), collagen deposition (Gomori's silver staining for reticulin collagen fibers), and immunohistochemistry for myofibroblast characterization were carried out based on the cellular expression of alpha-smooth muscle actin, vimentin, cytokeratin, E-cadherin, snail antigen homologue 1 (SNAI1) (Snail), and the cytokine expression of transforming growth factor-beta (TGF-ß). Parasitological screening was carried out using conventional polymerase chain reaction (PCR) and the immunohistochemical reaction of streptavidin-peroxidase for visualizing Leishmania amastigotes. Dogs naturally infected with L. infantum and experimentally infected with L. infantum BH401 strains showed intense interstitial pneumonitis characterized by thickening of the alveolar septa as a consequence of an intense diffuse and focal (plaques) chronic exudate of mononuclear cells associated with fibrogenesis. The expression of alpha-actin, vimentin, and TGF-ß was higher in the lung interstitium of all infected dogs than in the other two groups (BH46 strain and controls). Moreover, in both the naturally and experimentally infected dog (BH401 strain) groups, the expression of Snail was moderate to intense in contrast to the other groups. Based on these immunohistochemical results, we concluded that mesenchymal cells are active in promoting changes in the extracellular matrix in the lungs of dogs naturally and experimentally infected with L. infantum, but it depends on the virulence of the parasite.

Mir-155-5p targets TP53INP1 to promote proliferative phenotype in hypersensitivity pneumonitis lung fibroblasts.

Background: Hypersensitivity pneumonitis (HP) is an inflammatory disorder affecting lung parenchyma and often evolves into fibrosis (fHP). The altered regulation of genes involved in the pathogenesis of the disease is not well comprehended, while the role of microRNAs in lung fibroblasts remains unexplored. Methods: We used integrated bulk RNA-Seq and enrichment pathway bioinformatic analyses to identify differentially expressed (DE)-miRNAs and genes (DEGs) associated with HP lungs. In vitro, we evaluated the expression and potential role of miR-155-5p in the phenotype of fHP lung fibroblasts. Loss and gain assays were used to demonstrate the impact of miR-155-5p on fibroblast functions. In addition, mir-155-5p and its target TP53INP1 were analyzed after treatment with TGF-ß, IL-4, and IL-17A. Results: We found around 50 DEGs shared by several databases that differentiate HP from control and IPF lungs, constituting a unique HP lung transcriptional signature. Additionally, we reveal 18 DE-miRNAs that may regulate these DEGs. Among the candidates likely associated with HP pathogenesis was miR-155-5p. Our findings indicate that increased miR-155-5p in fHP fibroblasts coincides with reduced TP53INP1 expression, high proliferative capacity, and a lack of senescence markers compared to IPF fibroblasts. Induced overexpression of miR-155-5p in normal fibroblasts remarkably increases the proliferation rate and decreases TP53INP1 expression. Conversely, miR-155-5p inhibition reduces proliferation and increases senescence markers. TGF-ß, IL-4, and IL-17A stimulated miR-155-5p overexpression in HP lung fibroblasts. Conclusion: Our findings suggest a distinctive signature of 53 DEGs in HP, including CLDN18, EEF2, CXCL9, PLA2G2D, and ZNF683, as potential targets for future studies. Likewise, 18 miRNAs, including miR-155-5p, could be helpful to establish differences between these two pathologies. The overexpression of miR-155-5p and downregulation of TP53INP1 in fHP lung fibroblasts may be involved in his proliferative and profibrotic phenotype. These findings may help differentiate and characterize their pathogenic features and understand their role in the disease.

Varicela neonatal tardía: presentación en un paciente pediátrico / Late neonatalchickenpox: presentation in a pediatric patient

La varicela es una infección poco frecuente durante la gestación, el riesgo para el feto y las manifestaciones clínicas, variarán en función del momento del embarazo en que se produce la infección materna, cuando la erupción maculopapular materna se produce entre los 5 días previos al parto y las 48 horas posteriores, se habla de varicela neonatal tardía. La clínica es grave, con afectación visceral (pulmonar, cerebral, hepática, hemorragias cutáneas, etc.) y un 30 % de los casos desarrollarán una varicela fulminante. Se presenta el caso de neonato masculino que consultó por lesiones en piel, tipo pápulas eritematosas y vesiculares pleomorfas, de distribución dispersa. Con evolución clínica tórpida, permaneció 24 horas en la institución, con franco deterioro respiratorio y neurológico, compatible con cuadro de varicela neonatal tardía fulminante(AU)

Chickenpox is considered a rare infection during pregnancy, the risk to the fetus and the clinical manifestations will vary depending on the time of pregnancy when the maternal infection occurs, when the maternal maculo-papular injuries occurs within the previous 5 days after delivery and 48 hours after, there is talk of late neonatal chickenpox. The symptoms are severe with visceral involvement (lung, brain, liver, skin bleeding, etc.) and 30% of cases will develop fulminant chickenpox. We present the case of a male neonate who consults due to skin lesions, such as erythematous papules and pleomorphic vesicles, with scattered distribution. With a torpid clinical course, who remains in the institution for 24 hours, with frank respiratory and neurological deterioration compatible with late-neonatal fulminant varicella symptoms(AU)

Adaptive multi-interventional trial platform to improve patient care for fibrotic interstitial lung diseases.

BACKGROUND: Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of lung diseases associated with significant morbidity and mortality. Despite a large increase in the number of clinical trials in the last 10 years, current regulatory-approved management approaches are limited to two therapies that prevent the progression of fibrosis. The drug development pipeline is long and there is an urgent need to accelerate this process. This manuscript introduces the concept and design of an innovative research approach to drug development in fILD: a global Randomised Embedded Multifactorial Adaptive Platform in fILD (REMAP-ILD). METHODS: Description of the REMAP-ILD concept and design: the specific terminology, design characteristics (multifactorial, adaptive features, statistical approach), target population, interventions, outcomes, mission and values, and organisational structure. RESULTS: The target population will be adult patients with fILD, and the primary outcome will be a disease progression model incorporating forced vital capacity and mortality over 12 months. Responsive adaptive randomisation, prespecified thresholds for success and futility will be used to assess the effectiveness and safety of interventions. REMAP-ILD embraces the core values of diversity, equity, and inclusion for patients and researchers, and prioritises an open-science approach to data sharing and dissemination of results. CONCLUSION: By using an innovative and efficient adaptive multi-interventional trial platform design, we aim to accelerate and improve care for patients with fILD. Through worldwide collaboration, novel analytical methodology and pragmatic trial delivery, REMAP-ILD aims to overcome major limitations associated with conventional randomised controlled trial approaches to rapidly improve the care of people living with fILD.

Usual interstitial pneumopathy in a patient with hypersensitivity pneumonitis and microscopic polyangiitis. Case report.

One of the most frequent diffuse interstitial lung diseases is hypersensitivity pneumonitis. It is related to exposure to diverse antigens, causing fibrosis in advanced stages, making the differential diagnosis with interstitial pulmonary fibrosis difficult as it overlaps with the usual interstitial pneumonia pattern. On the other hand, there are interstitial lung diseases associated with ANCA, such as microscopic polyangiitis, which is also related to the usual interstitial pneumonia pattern. We present the case of a 74-year-old male patient with chronic dyspnea, history of smoking and exposure to organic particles, in addition to a pattern suggestive of moderately severe restriction. The diagnosis was confirmed by histology of hypersensitivity pneumonitis by presenting granules, however, anti MPO and p-ANCA positivity was found, integrating the simultaneous diagnosis of microscopic polyangiitis. This is a case of difficult diagnosis since these pathologies have not been previously reported to coexist.

Asma bronquial reagudizada y neumonitis por hipersensibilidad provocada por alergia a perros domésticos / Exacerbated Bronchial Asthma and Hypersensitivity Pneumonitis Triggered by Allergy to Domestic Dogs

Se presenta un caso clínico interpretado al principio como asma alérgica al pelo de perro y, luego, documentado como neumonitis por hipersensibilidad no fibrótica vinculada al antecedente ambiental doméstico.

We present a case initially interpreted as allergic asthma triggered by dog hair and later confirmed as non-fibrotic hypersensitivity pneumonitis (HP) associated with domestic environmental conditions.

Ecografía pulmonar y neumonitis por aspiración de queroseno

Introducción: La ingestión de queroseno conduce a la aparición de diversas complicaciones. Dada su baja viscosidad, en el sistema respiratorio es capaz de llegar a las vías aéreas distales y provocar lesión pulmonar, lo cual requiere atención urgente. La ecografía pulmonar, en la emergencia médica es un pilar que ha aumentado la capacidad de diagnóstico, guía la toma de decisiones y permite estratificar el pronóstico del paciente. Objetivo: Presentar un paciente con neumonitis química por aspiración de queroseno, sus características clínicas y procedimiento ecográfico pulmonar empleado. Caso clínico: Paciente masculino de 68 años de edad con antecedentes de alcoholismo y epilepsia, que hace tratamiento irregular. Asistió al servicio de urgencias con dificultad respiratoria de varios días de evolución y el precedente de ingesta de queroseno, con broncoaspiración. Se le realizó ecografía pulmonar, según el protocolo Bedside Lung Ultrasound in Emergency; se observó síndrome intersticio alveolar grave, engrosamiento de la línea pleural, microconsolidaciones subpleurales y pérdida grave de la aireación pulmonar. Se le instauró tratamiento con ventilación mecánica invasiva y antibiótico terapia; mejoró el puntaje de aireación pulmonar y el paciente se recuperó. Conclusiones: La insuficiencia respiratoria aguda secundaria a neumonitis química por queroseno, es una entidad clínica compleja en su evaluación; el uso de la ecografía pulmonar constituye una herramienta vital que permite valorar en tiempo real el parénquima pulmonar y la pleura, para tomar decisiones terapéuticas oportunas y precisas.

Introduction: The ingestion of kerosene leads to the appearance of various complications. Given its low viscosity, in the respiratory system, it is capable of reaching the distal airways and causing lung injury, which requires urgent attention. Lung ultrasound, in medical emergencies, is a pillar that has increased diagnostic capacity, guides decision-making and allows stratifying the patient's prognosis. Objective: To present a patient with chemical pneumonitis due to aspiration of kerosene, its clinical characteristics and pulmonary ultrasound procedure used. Clinical case: 68-year-old male patient with a history of alcoholism and epilepsy, which undergoes irregular treatment. He attended Emergency with respiratory distress of several days of evolution and the precedent of ingestion of kerosene, with bronchial aspiration. Lung ultrasound was performed, according to the Bedside Lung Ultrasound in Emergency protocol; severe alveolar interstitial syndrome, thickening of the pleural line, subpleural micro-consolidations, and severe loss of pulmonary aeration were observed. Treatment with invasive mechanical ventilation and antibiotic therapy was established; the pulmonary aeration score improved, and the patient recovered. Conclusions: Acute respiratory failure secondary to chemical pneumonitis due to kerosene is a complex clinical entity in its evaluation; the use of lung ultrasound is a vital tool that allows the lung parenchyma and pleura to be assessed in real time, in order to make timely and precise therapeutic decisions.

Radiation pneumonitis in relation to pulmonary function, dosimetric factors, TGFß1 expression, and quality of life in breast cancer patients receiving post-operative radiotherapy: a prospective 6-month follow-up study.

PURPOSE: To investigate development of radiation pneumonitis (RP) in relation to pulmonary function, dosimetric factors, and transforming growth factor beta-1 (TGFß1) expression in irradiated breast cancer patients. METHODS: A total of 49 breast cancer patients who received post-operative radiotherapy (RT) were evaluated in terms of pulmonary function tests (PFTs), quality of life (QoL), development of RP, dosimetric factors, cytokine levels, and lung high-resolution computed tomography (HRCT) before and after RT. ROC analysis was performed for performance of dosimetric factors in predicting RP, while frequencies of single nucleotide polymorphisms (SNPs) genotyped for TGFß1 (rs11466345 and rs1800470) were also evaluated. RESULTS: All cases with RP (10.2%) recovered clinically at the end of third post-RT month. PFT and HRCT parameters were similar before and after RT overall, as well as by RP and the radiation field subgroups. ROC analysis revealed the significant role of the ipsilateral V5 (cutoff value of 45.9%, p = 0.039), V10 (29.4%, p = 0.015), V20 (23%, p = 0.017), and MLD (1200 cGy, p = 0.030) in predicting RP. Higher post-RT TGFß1 levels (p = 0.037) were noted overall and in patients with RP. Patient and control groups were similar in terms of frequencies of SNPs genotyped for TGFß1 (rs11466345 and rs1800470). EORTC QLQ-C30 and QLQ-BR-23 scores were similar in patients with vs. without RP. CONCLUSION: Our findings revealed significant role of dosimetric factors including MLD, V20 as well as the low dose-volume metrics in predicting the risk of RP among breast cancer patients who received post-operative RT. Implementation of RT, extent of radiation field or the presence of RP had no significant impact on PFTs.

Lymphocytic Interstitial Pneumonia Associated with Sjögren Syndrome: Case-Based Review.

BACKGROUND: Few studies have described lymphocytic interstitial pneumonia (LIP) in Sjögren's syndrome (SS). We aimed to analyze the clinical, therapeutic, and outcome of patients with SS and LIP. METHODS: We searched for articles in PubMed/MEDLINE, LILACS, SciELO, and Cochrane from 1966 to 2020, in English, Spanish, French, Chinese, and Japanese literature had an English summary about LIP and SS. The keywords were "Sjögren syndrome" and "Lymphocytic interstitial pneumonia." Additionally, we report a patient with SS and LIP. RESULTS: 27 patients with SS and LIP were found. The age range ranged from 14 to 73 years old, with only 3 male patients, with a predominance of LIP cases in patients with primary SS (22/27). In the following case, the LIP preceded SS by 2 years; in the other 26 patients, SS preceded it. The majority presented dyspnea, mainly on exertion, followed by a dry cough. Lung biopsy was performed in 10 studies. Therapy varied from the use of clinical observation, corticosteroids alone, or associated with immunosuppressants. Most studies have shown improvement or stabilization of the pulmonary condition after therapy (13/16 studies). CONCLUSION: This article reviews cases of lymphocytic interstitial pneumonia associated with Sjögren syndrome and shows a good outcome with adequate treatment. It emphasizes that early LIP diagnosis in patients with Sjogren Syndrome may be determined using lung computed tomography.

Single Nucleotide Polymorphisms (SNP) and SNP-SNP Interactions of the Surfactant Protein Genes Are Associated With Idiopathic Pulmonary Fibrosis in a Mexican Study Group; Comparison With Hypersensitivity Pneumonitis.

Surfactant proteins (SPs) are important for normal lung function and innate immunity of the lungs and their genes have been identified with significant genetic variability. Changes in quantity or quality of SPs due to genetic mutations or natural genetic variability may alter their functions and contribute to the host susceptibility for particular diseases. Alternatively, SP single nucleotide polymorphisms (SNPs) can serve as markers to identify disease risk or response to therapies, as shown for other genes in a number of other studies. In the current study, we evaluated associations of SFTP SNPs with idiopathic pulmonary fibrosis (IPF) by studying novel computational models where the epistatic effects (dominant, additive, recessive) of SNP-SNP interactions could be evaluated, and then compared the results with a previously published hypersensitivity pneumonitis (HP) study where the same novel models were used. Mexican Hispanic patients (IPF=84 & HP=75) and 194 healthy control individuals were evaluated. The goal was to identify SP SNPs and SNP-SNP interactions that associate with IPF as well as SNPs and interactions that may be unique to each of these interstitial diseases or common between them. We observed: 1) in terms of IPF, i) three single SFTPA1 SNPs to associate with decreased IPF risk, ii) three SFTPA1 haplotypes to associate with increased IPF risk, and iii) a number of three-SNP interactions to associate with IPF susceptibility. 2) Comparison of IPF and HP, i) three SFTPA1 and one SFTPB SNP associated with decreased risk in IPF but increased risk in HP, and one SFTPA1 SNP associated with decreased risk in both IPF and HP, ii) a number of three-SNP interactions with the same or different effect pattern associated with IPF and/or HP susceptibility, iii) one of the three-SNP interactions that involved SNPs of SFTPA1, SFTPA2, and SFTPD, with the same effect pattern, was associated with a disease-specific outcome, a decreased and increased risk in HP and IPF, respectively. This is the first study that compares the SP gene variants in these two phenotypically similar diseases. Our findings indicate that SNPs of all SFTPs may play an important role in the genetic susceptibility to IPF and HP. Importantly, IPF and HP share some SP genetic variants, suggesting common pathophysiological mechanisms and pathways regarding surfactant biogenesis, but also some differences, highlighting the diverse underlying pathogenic mechanisms between an inflammatory-driven fibrosis (HP) and an epithelial-driven fibrosis (IPF). Alternatively, the significant SNPs identified here, along with SNPs of other genes, could serve as markers to distinguish these two devastating diseases.

A new biomarker in severe pneumonia associated with coronavirus disease 2019: hypoalbuminemia. A prospective study

ABSTRACT BACKGROUND: Effective triage and early detection are very important for controlling and treating coronavirus disease 2019 (COVID-19). Thus, the relationships between hypoalbuminemia and other acute-phase reactants in such cases need to be evaluated. OBJECTIVES: To investigate the importance of albumin levels in cases of severe pneumonia due to COVID-19. DESIGN AND SETTING: Prospective study conducted in Ankara City Hospital (a stage 3 hospital), Turkey. METHODS: Data from 122 patients diagnosed with pneumonia due to COVID-19 who were admitted to this hospital were analyzed statistically in comparison with date from 60 healthy controls. Three groups were established: healthy controls, intubated patients and non-intubated patients. Lung tomography scans from the patients were examined one-by-one. Real-time polymerase chain reaction (RT-PCR) test results were recorded. RESULTS: Albumin levels were statistically significantly lower in the intubated and non-intubated groups than in the control group, in comparing the three groups (P < 0.01). The other acute-phase reactants, i.e. neutrophil-to-lymphocyte ratio and C-reactive protein levels, were significantly higher in the intubated and non-intubated groups than in the control group (P < 0.05). Albumin levels were also significantly lower in the intubated group than in the non-intubated group (P = 0.02). No differences were detected with regard to other parameters (P > 0.05). CONCLUSIONS: Hypoalbuminemia may constitute a biomarker indicating the severity of pneumonia due to COVID-19.

Everolimus-Induced Pneumonitis in Patients with Neuroendocrine Neoplasms: Real-World Study on Risk Factors and Outcomes.

BACKGROUND: Everolimus-induced pneumonitis (EiP) has been poorly studied in patients with neuroendocrine neoplasms (NEN) outside clinical trials. The aim of this study was to evaluate the incidence, risk factors, and outcomes of EiP in patients with NENs using real-world data. METHODS: Retrospective study of everolimus-treated patients with advanced NENs. Imaging reports were systematically reviewed for the presence of pneumonitis. Clinical features and treatment profiles for EiP were summarized. Overall survival (OS) was calculated from the initiation of everolimus to the date of death or last follow-up using the Kaplan-Meier method. RESULTS: A total of 122 patients were included. Median age at start of everolimus was 62 (19-86) years, 62% (76/122) were male, and half were from pancreatic origin (62, 51%). Twenty-eight patients (23%) developed EiP: 82% grade (G)1 or G2, 14% G3 and 4% G4. The median time to EiP was 3.6 (0.8-51) months. Primary tumor site, concurrent lung disease, smoking history, and prior therapies were not associated with the onset of EiP. Patients who developed EiP had longer time on everolimus treatment (median 18 months vs 6 months; P = .0018) and OS (77 months vs 52 months; P = .093). Everolimus-induced pneumonitis was a predictor of improved OS by multivariable analysis (HR 0.39, 95% CI 0.19-0.82; P = .013). CONCLUSION: Everolimus-induced pneumonitis in the real-world clinical setting is present in one quarter of patients with NENs receiving everolimus and often occurs early. While risk factors for EiP were not identified, patients with EiP had improved survival.

A Short Course of Prednisolone in Patients With Moderate Covid 19 Respiratory Failure- Stop the Progression a Case Series.

Covid 19 positive patients requiring oxygen therapy to maintain saturations above 90% were given a trial of oral prednisolone between 15 and 30 mg until they were weaned to room air maintaining saturations >95%. This treatment resulted in the rapid resolution of worsening respiratory function of 4 Covid 19 positive patients within the High Dependency unit in a tertiary medical center. The cases are from the "first wave" in Trinidad, March 2020. The signs and symptoms of respiratory failure resolved after 72 hours of prednisolone treatment and none of these patients were escalated to non-invasive or invasive respiratory support. The patients were kept for a further 48 hours after the steroids were discontinued to monitor for relapse of symptoms, all patients were discharged home after quarantine. The initiation of a prednisolone steroid trial must be considered in Covid 19 positive patients needing supplementary oxygen therapy or developing worsening shortness of breath. Early Covid respiratory failure responds to a low dose for a short duration and prevents escalation to non-invasive/invasive respiratory support.

Impacto clínico de un grupo de discusión multidisciplinaria en el diagnóstico de fibrosis pulmonar idiopática en Colombia / Clinical impact of a multidisciplinary discussion group on the diagnosis of idiopathic pulmonary fibrosis in Colombia

Resumen Introducción: la fibrosis pulmonar idiopática (FPI) es una enfermedad pulmonar intersticial (EPID) de mal pronóstico, considerada huérfana en Colombia. Un diagnóstico correcto tiene implicaciones para el paciente y los costos de atención. Los grupos de discusión multidisciplinaria (GDM) se consideran el estándar de oro en el diagnóstico. No hay estudios previos en Colombia de la experiencia de un GDM. Objetivos: evaluar el impacto de un GDM en una institución de cuarto nivel en Bogotá en cambio de diagnóstico de pacientes con EPID y la concordancia entre el diagnóstico inicial y final de FPI. Material y métodos: pacientes con EPID evaluados entre 2015-2018 por el GDM conformado por neumólogos, radiólogo, patólogo y reumatólogos. Criterios ATS/ERS/JRS/ALAT de diagnóstico de FPI. Descripción del cambio en el diagnóstico y concordancia entre el diagnóstico inicial y del GDM en FPI. Resultados: de 165 pacientes con EPID se cambió el diagnóstico en 35.2%. En 77.3% pacientes con diagnóstico inicial de FPI y en 6.7% con diagnóstico inicial diferente a FPI el GDM confirmó FPI. Al descartar FPI, los principales diagnósticos fueron neumonitis de hipersensibilidad en fase crónica (29.4%) y neumonía intersticial no específica (23.5%). El índice kappa entre el diagnóstico inicial y final de FPI fue 0.71 (0.60-0.82). Conclusiones: el GDM en EPID tuvo un importante impacto clínico demostrado por un alto porcentaje de cambió del diagnóstico de remisión. Se descartó el diagnóstico inicial de FPI en un porcentaje significativo de pacientes y se ratificó en un grupo menor sin esta sospecha clínica inicial. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2017).

Abstract Introduction: idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease (ILD) with a poor prognosis, considered an orphan disease in Colombia. An accurate diagnosis has implications for the patient and healthcare costs. Multidisciplinary discussion groups (MDGs) are considered the gold standard for diagnosis. There are no prior studies in Colombia on the experience of an MDG. Objectives: to evaluate the impact of an MDG in a quaternary care institution in Bogotá on the change in the diagnosis of patients with ILD and the concordance between the initial and final diagnosis of IPF. Materials and methods: patents with ILD evaluated from 2015-2018 by the MDG made up of pulmonologists, a radiologist, a pathologist and rheumatologists. The ATS/ERS/JRS/ALAT diagnostic criteria for IPF. A description of changes in the diagnosis and the agreement between the initial diagnosis and the MDG diagnosis of IPF. Results: out of 165 patients with ILD, the diagnosis was changed in 32.5%. The MDG confirmed IPF in 77.3% of patients with an initial diagnosis of ILD and 6.7% of those with a different initial diagnosis. When IPF was ruled out, the main diagnoses were chronic hypersensitivity pneumonitis (24.8%) and nonspecific interstitial pneumonia (23.5%). The Kappa index between the initial and final IPF diagnoses was 0.71 (0.60-0.82). Conclusions: the MDG on ILD had a significant clinical impact evidenced by a high percentage of change in the referral diagnosis. The initial diagnosis of IPF was ruled out in a significant percentage of patients and confirmed in a smaller group which did not have this initial clinical suspicion. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2017).

Radiological and histological characteristics of patients with interstitial lung disease undergoing lung biopsy in a reference institution from eastern Colombia / Características radiológicas e histológicas de pacientes con enfermedad pulmonar intersticial llevados a biopsia pulmonar en una institución del oriente colombiano

Abstract Introduction: Interstitial lung disease (ILD) diagnosis requires a mukidisciplinary approach and, in some cases, lung biopsy. Objective: To describe the sociodemographic and clinical characteristics, as well as the radiological and histological findings, of patients with ILD who required lung biopsy after a mukidisciplinary board (pneumology, radiology, and pathology) of a reference center for respiratory diseases in Bucaramanga, Colombia, failed to reach the ILD diagnosis. Materials and methods: Cross-sectional study. The medical records of 56 patients treated at the Instituto Neumológico del Oriente who underwent lung biopsy between 2015 and 2019 were reviewed. Measures of central tendency and dispersion were calculated for demographic and clinical variables, respectively, to characterize them. A bivariate analysis was performed using Fisher's exact test to determine whether there were differences in the distribution of the sociodemographic and clinical variables according to the radiological patterns and the final histological diagnosis. Results: Participants' median age was 67 years (IQR: 59-72) and 55.35% were men. 43 patients had a radiological pattern inconsistent with usual interstitial pneumonia (UIP); 4 had a pattern consistent with possible UIP; and 9 had a pattern consistent with UIP. The most common histologic diagnoses were hypersensitivity pneumonitis (HP) (32.14%), nonspecific interstitial pneumonia (NSIP) (17.86%), and UIP (19.64%). Conclusion: In the study population, the primary reason for performing a lung biopsy was the presence of a radiologic pattern inconsistent with UIP, with HP being the predominant histopathological diagnosis. This is the first study to characterize patients with ILD who underwent lung biopsy in eastern Colombia, making a significant contribution to our understanding of the disease's epidemiology in the country.

Resumen Introducción. El diagnóstico de la enfermedad pulmonar intersticial (EPI) requiere un enfoque multidisciplinar y, en ocasiones, de una biopsia pulmonar. Objetivo. Describir las características sociodemográficas y clínicas, y los hallazgos radiológicos e histológicos de pacientes con EPI que requirieron biopsia pulmonar luego de no lograrse un diagnóstico de esta enfermedad por la junta médica multidisciplinar (neumología, radiología y patología) de un centro de referencia en enfermedades respiratorias de Bucaramanga, Colombia. Materiales y métodos. Estudio transversal. Se revisaron las historias clínicas de 56 pacientes atendidos en el Instituto Neumológico del Oriente y que fueron remitidos a biopsia pulmonar entre 2015 y 2019. Se analizaron variables demográficas y clínicas, calculando medidas de tendencia central y de dispersión para su respectiva caracterización. Se realizó un análisis bivariado mediante test exacto de Fisher para determinar si existían diferencias en la distribución de las variables sociodemográficas y clínicas de acuerdo con los patrones radiológicos y el diagnóstico histológico definitivo. Resultados. La mediana de edad fue 67 años (RIC: 59-72), 55.35% fueron hombres. 43 pacientes presentaron patrón radiológico inconsistente con neumonía intersticial usual (NIU); 4, patrón de posible NIU y, 9, patrón de NIU. Los diagnósticos histológicos más frecuentes fueron neumonitis por hipersensibilidad (NH) (32.14%), neumonía intersticial no específica (17.86%) y NIU (19.64%). Conclusión. La principal razón para realizar biopsia pulmonar en la población de estudio fue la presencia de un patrón radiológico inconsistente con NIU, siendo la NH el principal diagnóstico histopatológico. Este es el primer trabajo que caracteriza a pacientes con EPI del oriente colombiano llevados a biopsia pulmonar, lo que representa un importante aporte al conocimiento de la epidemiología de esta enfermedad en Colombia.

Hypersensitivity Pneumonitis: Diagnostic and Therapeutic Challenges.

Hypersensitivity pneumonitis (HP) is one of the most common interstitial lung diseases (ILD), that presents unique challenges for a confident diagnosis and limited therapeutic options. The disease is triggered by exposure to a wide variety of inciting antigens in susceptible individuals which results in T-cell hyperactivation and bronchioloalveolar inflammation. However, the genetic risk and the pathogenic mechanisms remain incompletely elucidated. Revised diagnostic criteria have recently been proposed, recommending to classify the disease in fibrotic and non-fibrotic HP which has strong therapeutic and outcome consequences. Confident diagnosis depends on the presence of clinical features of ILD, identification of the antigen(s), typical images on high-resolution computed tomography (HRCT), characteristic histopathological features, and lymphocytosis in the bronchoalveolar lavage. However, identifying the source of antigen is usually challenging, and HRCT and histopathology are often heterogeneous and not typical, supporting the notion that diagnosis should include a multidisciplinary assessment. Antigen removal and treating the inflammatory process is crucial in the progression of the disease since chronic persistent inflammation seems to be one of the mechanisms leading to lung fibrotic remodeling. Fibrotic HP has a few therapeutic options but evidence of efficacy is still scanty. Deciphering the molecular pathobiology of HP will contribute to open new therapeutic avenues and will provide vital insights in the search for novel diagnostic and prognostic biomarkers.

[Girl with hypersensitivity pneumonitis. A case report]. / Niña con neumonitis por hipersensibilidad. Reporte de un caso.

BACKGROUND: Hypersensitivity pneumonitis entails several inflammatory lung diseases that preferentially affect the alveolar and perialveolar tissue. It is a very rare disease in children, with a complicated diagnosis due to the fact that antigen exposure usually goes unnoticed. CASE REPORT: A 12-year-old girl with dry cough, dyspnea, wheezing, and tachypnea, with partial improvement after treatment with inhaled bronchodilators and corticoids. The spirometry showed a restrictive pattern and reduced lung diffusion capacity; in the CT scan, centrilobular ground-glass opacities were observed, and a lymphocyte count of CD4/CD8 of 2.46 (lymphocytosis) was obtained from the bronchoalveolar lavage. IgG positivity to bird feathers was obtained. CONCLUSIONS: The treatment of hypersensitivity pneumonitis is based on avoiding exposure to the causative agent, which is determined by the prognosis; for which taking an extensive medical history is of paramount importance. Corticosteroids can be prescribed based on the clinical response, the pulmonary function, and the radiological improvement.

Antecedentes: La neumonitis por hipersensibilidad agrupa varias enfermedades inflamatorias pulmonares que afectan preferentemente el tejido alveolar y perialveolar. En niños se trata de una enfermedad muy rara, con diagnóstico complicado debido a que la exposición antigénica suele pasar desapercibida. Caso clínico: Niña de 12 años que presentaba tos seca, disnea, sibilancias y taquipnea con mejoría parcial al tratamiento con broncodilatadores y corticoides inhalados. En la espirometría presentó un patrón restrictivo y una capacidad de difusión pulmonar reducida; en la tomografía computarizada se observaron opacidades centrolobulillares en vidrio esmerilado y del lavado broncoalveolar se obtuvo un cociente de linfocitosis CD4/CD8 de 2.46. Se obtuvo IgG positiva a plumas de aves. Conclusiones: El manejo de la neumonitis por hipersensibilidad se basa en evitar la exposición al agente causante, lo que determina el pronóstico; de ahí que resulta de vital importancia realizar una historia clínica exhaustiva. Pueden indicarse corticosteroides en función de la respuesta clínica, la función pulmonar y la mejoría radiológica.

Consolidative stereotactic ablative radiotherapy (SABR) to intrapulmonary lesions is associated with prolonged progression-free survival and overall survival in oligometastatic NSCLC patients: A prospective phase 2 study.

OBJECTIVES: Stereotactic Ablative Radiotherapy (SABR) has shown high rates of local control and prolonged survival in early-stage non-small cell lung cancer (NSCLC), though its role in oligometastatic disease is undefined. This study aimed to evaluate SABR as a local consolidative therapy (LCT) in oligometastatic NSCLC patients. METHODS: In this prospective, single-arm phase 2 trial, we sought to evaluate SABR in patients with stage IV NSCLC, with ≤ five lesions, including the primary tumor. Patients received initial systemic therapy according to international guidelines. Patients without progression after front-line therapy (two months of targeted therapy and ≥ four cycles of chemotherapy) were evaluated by an 18F-FDG-PET/CT to receive consolidative SABR (45-60 Gy in 3-5 fractions) to the primary and all intrapulmonary metastatic sites. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS) and toxicity. RESULTS: A total of 47 patients were included. Mean age was 58.9 years, 59.6 % were female, 87.2 % had adenocarcinoma histology, and the contralateral lung was the main site of metastases in 42.6 %. All patients received systemic front-line therapy, chemotherapy in 61.7 %, and a tyrosine kinase inhibitor (TKI) in 38.3 %. Disease control rate (DCR) and complete metabolic response (CMR) to SABR were 93.6 % and 70.2 %. Median PFS was 34.3 months (95 %CI; 31.1-38.8) for the total cohort; patients with a CMR had a median PFS of 53.9 monthsvs.31.9 months in those without CMR (p = 0.011). Median OS was not reached.Grade 1, 2, and 3 pneumonitis were observed in 79.5 % (31/39), 12.8 % (5/39) and 7.7 % (3/39), respectively. No grade ≥4 toxicities were observed. CONCLUSION: The use of SABR as LCT in oligometastatic NSCLC patients was well tolerated and showed favorable results regarding PFS and OS compared with historical data. The benefit was significantly higher in patients who reached a CMR as assessed by 18F-FDG-PET/CT.

Herpes simplex Virus Pneumonitis in an Acute/Subacute Paracoccidioidomycosis Patient With Malabsorption Syndrome. Case-Report and Literature Review.

Paracoccidioides sp.-Herpes simplex virus (HSV) co-infection was not reported until now and malabsorption syndrome is a rare complication of the acute/subacute form (AF) of paracoccidioidomycosis (PCM), characterized by life-threatening abnormalities, such as fat and protein loss, lymphopenia, ascites, and intense immunosuppression. A 21-year-old woman presented the PCM AF with intense involvement of the abdominal and intestinal lymphoid organs, which leads to the malabsorption syndrome and severe immunosuppression. This patient developed a fatal-disseminated HSV infection associated with the paracoccidioidal disease. This case demonstrates that, in addition to the antigen-specific immunosuppression, some PCM patients can present a generalized cell-mediated immune depression and endogenous infection of latent microorganisms. On the best of our knowledge, this is the first report of an association between PCM and HSV infection.