Severe cryptogenic bronchiolitis: Case report.

Bronchiolitis obliterans (BO) is a progressive fibrotic process that predominantly affects the small airways and is identified as constrictive bronchiolitis by pathologists. It is commonly associated with allogeneic hematopoietic stem cell transplant (HSCT), lung transplant, exposure to inhaled toxins, post-infectious processes, autoimmune diseases, and sometimes, no known cause. In the latter case, it is referred to as cryptogenic bronchiolitis obliterans. A 52-year-old Hispanic man with a medical history of hypertension, diabetes mellitus, and coronary artery disease was referred to the pulmonary department due to experiencing dyspnea on exertion, intermittent dry cough, and progressive limitation of activities of daily living. Spirometry revealed severe obstructive changes, and chest high-resolution computed tomography showed ground-glass opacities with nodular infiltrates in the upper lobes, leading to a presumptive diagnosis of hypersensitivity pneumonitis. The patient underwent a lung surgical biopsy of the right upper and lower lobes, which revealed extensive constrictive bronchiolitis. Due to the patient's worsening general condition, bilateral lung transplantation succeeded without any further complications. Following the transplantation, the patient showed good recovery and functional improvement. Bronchiolitis obliterans, or constrictive bronchiolitis, has a variable natural history. It is associated with a higher risk of mortality in allogenic HSCT. When BO is secondary to inhalation of toxic gases, it is usually nonprogressive and limited to toxin exposure. Autoimmune diseases or cryptogenic bronchiolitis are rare and have a heterogeneous clinical course. To make a proper diagnosis, clinical history, radiologic and histologic findings must be considered.

Small airway disease in post-acute COVID-19 syndrome, a non-conventional approach in three years follow-up of a patient with long COVID: a case report.

BACKGROUND: Small airways disease (SAD), a novel finding described in post-acute COVID-19 patients, should be suspected when respiratory symptoms continue, air trapping persists on expiratory CT scans, and imaging findings fail to improve despite objectively better conventional pulmonary function test (PFT) parameters. The forced oscillation technique (FOT) and Multiple breathing washout (MBW) are both very sensitive methods for detecting anomalies in the peripheral airways. CASE PRESENTATION: We discuss the case of a 60-year-old Hispanic patient who had severe COVID-19 pneumonia and developed dyspnea, fatigue, and limited daily activity a year later. The PFTs revealed restrictive lung disease, as seen by significant diffusing capacity of the lungs for carbon monoxide (DLCO) decrease, severe desaturation, and poor 6-min walk test (6MWT) performance. The patient was treated with lowering corticosteroids as well as pulmonary rehabilitation (PR). During the 24-month follow-up, the dyspnea and fatigue persisted. On PFTs, 6MWT performance and restricted pattern improved slightly, but MBW discovered significant ventilatory inhomogeneity. FOT revealed substantial peripheral airway obstructive abnormalities. On CT scans, air trapping and ground-glass opacities (GGO) improved somewhat. The patient used a bronchodilator twice a day and low-dose inhaled corticosteroids (160 µg of budesonide and 4.5 µg of formoterol fumarate dihydrate) for nine months. PR sessions were resuming. The restricting parameters were stabilized and the DLCO had normalized after 36 months, with a 6MWT performance of 87% but significant desaturation. The CT scan revealed traction bronchiectasis, low GGO, and persistent air trapping. Without normalization, FOT and MBW scores improved, indicating small airway disease. CONCLUSIONS: The necessity of integrating these tests when detecting SAD is emphasized in our paper. This article lays the foundation for future research into the best ways to manage and monitor SAD in post-acute COVID-19 patients.

[Small airway: from definition to treatment]. / Vía aérea pequeña: de la definición al tratamiento.

The small airway, present since the origins of humanity and described barely a century ago, has recently been discovered as the anatomical site where inflammation begins in some obstructive lung diseases, such as asthma and Chronic Obstructive Pulmonary Disease (COPD), per se. Small airway dysfuction was identified in up to 91% of asthmatic patients and in a large proportion of COPD patients. In subjects without pathology, small airway represent 98.8% (approximately 4500 ml) of the total lung volume, contributing only between 10-25% of the total lung resistance; however, in subjects with obstruction, it can represent up to 90% of the total resistance. Despite this, its morphological and functional characteristics allow its dysfunction to remain undetected by conventional diagnostic methods, such as spirometry. Hence the importance of this review, which offers an overview of the tools available to assess small airway dysfunction and the possible therapies that act in this silent zone.

La vía aérea pequeña, presente desde los orígenes de la humanidad y descrita hace apenas un siglo, se ha descubierto recientemente como el sitio anatómico donde inicia la inflamación provocada por algunas enfermedades pulmonares obstructivas: asma y enfermedad pulmonar obstructiva crónica (EPOC), per se. Se ha identificado disfunción de la vía aérea pequeña en el 91% de los pacientes asmáticos y en una gran proporción de quienes padecen EPOC. En los pacientes sin enfermedad, la vía aérea pequeña representa el 98.8% (4500 mL) del volumen pulmonar total, y solo aporta del 10 al 25% de la resistencia pulmonar total; sin embargo, en sujetos con obstrucción puede suponer el 90% de la resistencia total. A pesar de esto, sus características morfológicas y funcionales permiten que la disfunción pase inadvertida por métodos diagnósticos convencionales, por ejemplo la espirometría. Con base en lo anterior, el objetivo de este estudio fue revisar el panorama general de los métodos disponibles para evaluar la vía aérea pequeña y los posibles tratamientos asociados con esta zona silente.

Ventilation dynamics using a portable device coupled to the six-minute walk test in people with long-COVID syndrome: a preliminary study.

OBJECTIVE: To investigated the dynamic ventilatory responses and their influence on functional exercise capacity in patients with long-COVID-19 syndrome (LCS). RESULTS: Sixteen LCS patients were subjected to resting lung function (spirometry and respiratory oscillometry-RO) and cardiopulmonary performance to exercise (Spiropalm®-equipped six-minute walk test-6MWT and cardiopulmonary exercise test-CPX). At rest, spirometry showed a normal, restrictive and obstructive pattern in 87.5%, 6.25% and 6.25% of participants, respectively. At rest, RO showed increased resonance frequency, increased integrated low-frequency reactance and increased difference between resistance at 4-20 Hz (R4-R20) in 43.7%, 50%, and 31.2% of participants, respectively. The median of six-minute walking distance (DTC6) was 434 (386-478) m, which corresponds to a value of 83% (78-97%) of predicted. Dynamic hyperinflation (DH) and reduced breathing reserve (BR) were detected in 62.5% and 12.5% of participants, respectively. At CPX, the median peak oxygen uptake (VO2peak) was 19 (14-37) ml/kg/min. There was a significant correlation of 6MWD with both R4-R20 (rs=-0.499, P = 0.039) and VO2peak (rs=0.628, P = 0.009). Our results indicate that DH and low BR are contributors to poor exercise performance, which is associated with peripheral airway disease. These are promising results considering that they were achieved with simple, portable ventilatory and metabolic systems.

Can home rehabilitation impact impulse oscillometry and lung ultrasound findings in patients with scleroderma-associated interstitial lung disease? A pilot study.

OBJECTIVE: Exercise has been demonstrated to be beneficial for improving physical capacity and quality of life in people with scleroderma, although knowledge of its impact on the respiratory system is limited. This study evaluated the impact of therapist-oriented home rehabilitation (TOHR) on impulse oscillometry (IOS) and lung ultrasound (LUS) findings in patients with scleroderma-associated interstitial lung disease (ILD). RESULTS: Twelve women with scleroderma underwent spirometry, IOS, and LUS before and after performing TOHR. Regarding spirometry, a normal pattern and restrictive damage were observed in five (41.7%) and seven (58.3%) participants pre-TOHR and post-TOHR, respectively. For IOS, an abnormal result was detected in nine (75%) pre-TOHR participants and six (50%) post-TOHR participants. Heterogeneity of resistance between 4-20 Hz (R4-R20) > 20% of the predicted value was observed in eight (66.7%) pre-TOHR participants and three (25%) post-TOHR participants (P = 0.031). An abnormal LUS result was observed in nine (75%) participants both pre-TOHR and post-TOHR. The main change observed was B-lines > 2, which was noted in nine (75%) participants both pre-TOHR and post-TOHR. Our findings suggest that TOHR for women with scleroderma-associated ILD improves the resistance and reactance measured by IOS, including small airway disease. Trial Registration ClinicalTrials.gov ID: NCT05041868 Registered on: 13th September 2021.

Acute lung injury secondary to hydrochloric acid instillation induces small airway hyperresponsiveness.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure characterized by altered lung mechanics and poor oxygenation. Bronchial hyperresponsiveness has been reported in ARDS survivors and animal models of acute lung injury. Whether this hyperreactivity occurs at the small airways or not is unknown. OBJECTIVE: To determine ex-vivo small airway reactivity in a rat model of acute lung injury (ALI) by hydrochloric acid (HCl) instillation. METHODS: Twelve anesthetized rats were connected to mechanical ventilation for 4-hour, and randomly allocated to either ALI group (HCl intratracheal instillation; n=6) or Sham (intratracheal instillation of 0.9% NaCl; n=6). Oxygenation was assessed by arterial blood gases. After euthanasia, tissue samples from the right lung were harvested for histologic analysis and wet-dry weight ratio assessment. Precision cut lung slice technique (100-200 µm diameter) was applied in the left lung to evaluate ex vivo small airway constriction in response to histamine and carbachol stimulation, using phase-contrast video microscopy. RESULTS: Rats from the ALI group exhibited hypoxemia, worse histologic lung injury, and increased lung wet-dry weight ratio as compared with the sham group. The bronchoconstrictor responsiveness was significantly higher in the ALI group, both for carbachol (maximal contraction of 84.5±2.5% versus 61.4±4.2% in the Sham group, P<0.05), and for histamine (maximal contraction of 78.6±5.3% versus 49.6±5.3% in the Sham group, P<0.05). CONCLUSION: In an animal model of acute lung injury secondary to HCL instillation, small airway hyperresponsiveness to carbachol and histamine is present. These results may provide further insight into the pathophysiology of ARDS.

Does the nitrogen single-breath washout test contribute to detecting pulmonary involvement in rheumatoid arthritis? A pilot study.

OBJECTIVE: There has been growing interest in studying small airway disease through measures of ventilation distribution, thanks to the resurgence of the nitrogen single-breath washout (N2SBW) test. Therefore, this study evaluated the contribution of the N2SBW test to the detection of pulmonary involvement in patients with rheumatoid arthritis (RA). RESULTS: Twenty-one patients with RA underwent clinical evaluation, pulmonary function tests (PFTs), including the N2SBW test, and computed tomography (CT). The main tomographic findings were air trapping and bronchiectasis (57.1% and 23.8% of cases, respectively). According to the phase III slope of the N2SBW (phase III slope), 11 and 10 patients had values < 120% predicted and > 120% predicted, respectively. Five patients with limited involvement on CT had a phase III slope > 120%. The residual volume/total lung capacity ratio was significantly different between patients with phase III slopes < 120% and > 120% (P = 0.024). Additionally, rheumatoid factor positivity was higher in patients with a phase III slope > 120% (P = 0.021). In patients with RA and airway disease on CT, the N2SBW test detects inhomogeneity in the ventilation distribution in approximately half of the cases, even in those with normal conventional PFT results.

SMALLa AIRWAY DISEASE IN COPD ASSOCIATED TO BIOMASS EXPOSURE.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous entity that may result from different causative agents and risk factors and may follow diverse clinical courses, including COPD secondary to biomass smoke exposure. At present, this phenotype is becoming more important for two reasons: first, because at least almost half of the world's population is exposed to biomass smoke, and second, because the possibility of it being diagnosed is increasing. Biomass smoke exposure COPD affects primarily women and is related with insults to the airways occurred during early life. Although constituents of biomass smoke and tobacco smoke are similar, the physiopathological changes they induce differ depending not only on the chemical composition (related with the type of fuel used) but also on the particle size and the inhalation pattern. Evidence has shown that biomass smoke exposure affects the airway, predominantly the small airways causing anthracofibrosis and peribronchiolar fibrosis changes that will clinically translate into chronic bronchitis symptoms, with a high impact on the quality of life. In this review, we focus especially on the main epidemiological and clinical differences between COPD secondary to biomass exposure and COPD caused by tobacco exposure.

Small airway disease in COPD associated to biomass exposure

Abstract Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous entity that may result from different causative agents and risk factors and may follow diverse clinical courses, including COPD secondary to biomass smoke exposure. At present, this phenotype is becoming more important for two reasons: first, because at least almost half of the world’s population is exposed to biomass smoke, and second, because the possibility of it being diagnosed is increasing. Biomass smoke exposure COPD affects primarily women and is related with insults to the airways occurred during early life. Although constituents of biomass smoke and tobacco smoke are similar, the physiopathological changes they induce differ depending not only on the chemical composition (related with the type of fuel used) but also on the particle size and the inhalation pattern. Evidence has shown that biomass smoke exposure affects the airway, predominantly the small airways causing anthracofibrosis and peribronchiolar fibrosis changes that will clinically translate into chronic bronchitis symptoms, with a high impact on the quality of life. In this review, we focus especially on the main epidemiological and clinical differences between COPD secondary to biomass exposure and COPD caused by tobacco exposure.

Computed tomography in hypersensitivity pneumonitis: main findings, differential diagnosis and pitfalls.

INTRODUCTION: Hypersensitivity pneumonitis (HP) is a disease with variable clinical presentation in which inflammation in the lung parenchyma is caused by the inhalation of specific organic antigens or low molecular weight substances in genetically susceptible individuals. Alterations of the acute, subacute and chronic forms may eventually overlap, and the diagnosis based on temporality and presence of fibrosis (acute/inflammatory HP vs. chronic HP) seems to be more feasible and useful in clinical practice. Differential diagnosis of chronic HP with other interstitial fibrotic diseases is challenging due to the overlap of the clinical history, and the functional and imaging findings of these pathologies in the terminal stages. Areas covered: This article reviews the essential features of HP with emphasis on imaging features. Moreover, the main methodological limitations of high-resolution computed tomography (HRCT) interpretation are discussed, as well as new perspectives with volumetric quantitative CT analysis as a useful tool for retrieving detailed and accurate information from the lung parenchyma. Expert commentary: Mosaic attenuation is a prominent feature of this disease, but air trapping in chronic HP seems overestimated. Quantitative analysis has the potential to estimate the involvement of the pulmonary parenchyma more accurately and could correlate better with pulmonary function results.

Reference Equations for Impulse Oscillometric and Respiratory System Model Parameters in Anglo and Hispanic Children / Ecuaciones de referencia para parámetros de oscilometría de impulsos y de modelo del sistema respiratorio en niños anglos e hispanos

Abstract The Impulse Oscillometry System (IOS) has been recognized as a useful diagnostic tool. Previous research by our group has shown that R5 (Resistance at 5 Hz), R5-R20 (frequency dependence of resistance), AX (the "Goldman Triangle") and the extended Resistor-Inductor-Capacitor (eRIC) model-derived parameter Cp (peripheral Compliance) are reliable measures that track respiratory system function. Here we determined the predictive equations from 112 asthmatic and non-asthmatic Anglo and Hispanic children data, that were previously classified into four groups: Normal, PSAI (Probable Small Airway Impairment), SAI (Small Airway Impairment), and Asthma by using regression analysis of IOS and eRIC model parameters as dependent variables regressed against age, height, and weight. Height showed the greatest correlation with IOS and eRIC model parameters and provided the most significant reference values for these measures in Anglo and Hispanic children. These values could serve as a useful framework for diagnosis, early interventions, and treatment of respiratory diseases in this population.

Resumen El Sistema de Oscilometría Impulsos (por sus siglas en Inglés: IOS) ha sido reconocido como una herramienta de diagnóstico útil. Investigaciones previas realizadas por nuestro grupo han demostrado que R5 (Resistencia a 5 Hz), R5-R20 (dependencia a la frecuencia de la resistencia), AX (el "Triángulo de Goldman") y el párametro Cp (Capacitancia periférica) derivado del modelo extendido Resistencia-inductor-condensador (eRIC) son medidas fiables que monitorean la función del sistema respiratorio. El presente estudio determina las ecuaciones de predicción de 112 niños Anglo e Hispanos asmáticos y no asmáticos, que previamente clasificados en cuatro grupos: Normal, PSAI (por su nombre en inglés: Probable daño en las vías aéreas menores), SAI (por su nombre en inglés: Daño en las vías aéreas menores), y Asma. Las ecuaciones de predicción se determinaron mediante análisis de regresión de parámetros del IOS y del modelo eRIC (variables dependientes) contra edad, estatura y peso. La estatura mostró la mejor correlación con los parámetros del IOS y del modelo eRIC, proporcionando los valores de referencia más significativos para estas medidas en niños Anglos e Hispanos. Estos valores podrían servir como un marco de referencia útil para el diagnóstico, intervenciones tempranas, y tratamiento de las enfermedades respiratorias en esta población.