Longstanding hypersensitivity pneumonitis and its response to roflumilast: A review of its likely immunological effects.

We describe the case of a 42yr old man with evidence of hypersensitivity pneumonitis referred with cough and breathlessness for several years which had further deteriorated in the prior 12 months. He had known atopic asthma without evidence of activation. A chest CT scan showed widespread ground glass change in his lung fields. He had feather bedding at home and in his youth cleaned aviaries. His forced vital capacity and lung volumes were reduced along with oxygen saturations at rest (92% on air), overnight (83% on air) and upon walking (78%). Steroids were commenced for a total of 6 months with little consistent improvement in symptoms or objective measures and with no change in his CT scan appearance. As a result, a trial of roflumilast (a phosphodiesterase-4 inhibitor) was commenced due to its range of immunological effects and in order to avoid long-term immune suppression with mycophenolate motefil in a young patient. On roflumilast treatment his cough and breathlessness improved at 4 weeks and the chest crackles cleared. An interval Chest CT scan showed resolution of the ground glass change with improved CT scores that are maintained 2 yrs. All oxygen measures improved and nocturnal oxygen was discontinued. His Lung function has remained largely stable on roflumilast and symptoms of cough and breathlessness have resolved. This case report reviews the immunology of hypersensitivity pneumonitis and the likely actions of Roflumilast relevant to this condition. It is the first published case report documenting its use in hypersensitivity pneumonitis.

Echocardiographic signs of pulmonary hypertension in patients with newly recognized hypersensitivity pneumonitis, prevalence and clinical predictors.

BACKGROUND: Hypersensitivity pneumonitis (HP) is the third, according to frequency, interstitial lung disease, with the estimated incidence rate of 1-2/100,000. In HP patients, the extensive inflammatory lesions encompassing both small airways and lung parenchyma, as well as subsequent development of lung fibrosis, may result in respiratory insufficiency and secondary pulmonary hypertension (PH). The aim of the present retrospective study was to assess the prevalence of echocardiographic signs of PH and its' clinical predictors, in newly recognized HP patients. METHODS: Consecutive HP patients, recognized in single pulmonary unit between 2005 and 2017, in whom echocardiography was performed at diagnosis, entered the present study. HP diagnosis was verified in every patient according to current diagnostic recommendations. The results of high resolution computed tomography of the chest (HRCT) were re-evaluated by two independent radiologists, blinded to clinical data. Echocardiographic signs of PH were defined as pulmonary artery systolic pressure (PASP) exceeding 36 mmHg. Regression analysis was applied to calculate PH risk, and receiver operator characteristic curves (ROC) were plotted to investigate diagnostic utility of various parameters in PH prediction. RESULTS: PASP exceeding 36 mmHg was noted in 26 out of 70 patients (37%)-with equal frequency among patients with fibrotic and non-fibrotic HP. Significant predictors of PH on echocardiography were: partial oxygen tension in arterialized capillary blood (PaO2) <69 mmHg, lung transfer capacity for carbon monoxide (TLCO) <42% of predicted, six minutes walking test (6MWT) distance <455 meters, and 6MWT desaturation rate >8%. In case of TLCO <42% of predicted, probability of PH on echocardiography was increased by five-fold, in case of 6MWT desaturation rate >8%-by four fold. CONCLUSIONS: The best predictors of PASP >36 mmHg on echocardiography in HP patients at diagnosis were: TLCO <42% and 6MWT desaturation rate >8%. Neither the presence of lung fibrosis on HRCT, nor the duration of the disease or patients age, were helpful in PH prediction.

Residual ground glass opacities three months after Covid-19 pneumonia correlate to alteration of respiratory function: The post Covid M3 study.

INTRODUCTION: Lung function in survivors of SARS-Co-V2 pneumonia is poorly known, but concern over the possibility of sequelae exists. METHODS: Retrospective study on survivors with confirmed infection and pneumonia on chest-CT. Correlations between PFT and residual radiologic anomalies at three months taking into account initial clinical and radiological severity and steroid use during acute phase. RESULTS: 137 patients (69 men, median age 59 (Q1 50; Q3 68), BMI 27.5 kg/m2 (25.1; 31.7)) were assessed. Only 32.9% had normal PFT, 75 had altered DLCO. Median (Q1; Q3) values were: VC 79 (66; 92) % pred, FEV1 81 (68; 89), TLC 78 (67; 85), DLCO 60 (44; 72), and KCO 89 (77; 105). Ground glass opacities (GGO) were present in 103 patients (75%), reticulations in 42 (30%), and fibrosis in 18 (13%). There were significantly lower FEV1 (p = 0.0089), FVC (p = 0.0010), TLC (p < 0.0001) and DLCO (p < 0.0001) for patients with GGO, lower TLC (p = 0.0913) and DLCO (p = 0.0181) between patients with reticulations and lower FVC (p = 0.0618), TLC (p = 0.0742) DLCO (p = 0.002) and KCO (p = 0.0114) between patients with fibrosis. Patients with initial ≥50% lung involvement had significantly lower FEV1 (p = 0.0019), FVC (p = 0.0033), TLC (p = 0.0028) and DLCO (p = 0.0003) compared to patients with ≤10%. There was no difference in PFT and residual CT lesions between patients who received steroids and those who did not. CONCLUSION: The majority of patients have altered PFT at three months, even in patients with mild initial disease, with significantly lower function in patients with residual CT lesions. Steroids do not seem to modify functional and radiological recovery. Long-term follow-up is needed.

Renal BOLD MRI in patients with chronic kidney disease: comparison of the semi-automated twelve layer concentric objects (TLCO) and manual ROI methods.

OBJECTIVE: Blood oxygenation level dependent (BOLD) MRI technique is used to evaluate changes in intra-renal oxygenation in chronic kidney disease (CKD). The purpose of this study was to evaluate if the novel twelve layer concentric objects (TLCO) method has advantages over the manually defined regions of interest (ROI) analysis. METHODS AND MATERIALS: Existing renal BOLD MRI data acquired before and after furosemide on a 3 T scanner from 41 CKD patients and 13 age matched healthy controls were analyzed using TLCO method and compared with previously reported ROI analysis. RESULTS: Regional R2* measurements were strongly correlated between the two methods, while ΔR2* was moderately correlated. Medullary R2* by ROI analysis showed higher values compared to R2*_Inner by TLCO, probably due to the contributions from the cortex to R2*_Inner. R2*_Slope and Δ(R2*_Slope), unique parameters based on the TLCO method provided the most significant differences between stage 3a CKD patients and controls and were correlated with eGFR. DISCUSSION: There was a high degree of agreement between the two methods in terms of regional R2* measurements and both methods did not show differences between moderate CKD patients and controls. However, R2*_Slope and Δ(R2*_Slope) showed the largest sensitivity in distinguishing CKD from controls.

Intraoperative oxygen challenge for toleration of single lung ventilation in a patient with severe obstructive airway disease: A case report.

Perioperative risk assessment is complex in patients with chronic obstructive pulmonary disease who have undergone previous lung resection surgery. A 70-year-old female with severe chronic obstructive pulmonary disease and previous right middle and lower lobectomy, presented for left lower lobe superior segmentectomy. Respiratory function tests revealed a forced expiratory volume in 1 second of 0.72L, a forced vital capacity of 1.93L, and a carbon monoxide transfer factor of 10.0 ml/min/mmHg. A cardiopulmonary exercise test demonstrated little ventilatory reserve with profound arterial desaturation on peak exercise, however, a normal peak oxygen consumption (16.7 ml/min/kg) and a nadir minute ventilation/carbon dioxide slope of 24 implied a limited risk of perioperative cardiovascular morbidity. Given these conflicting results we performed an intraoperative oxygen challenge test under general anaesthesia with sequential ventilation of different lobes of the lung. We demonstrate the use of the oxygen challenge test as an effective intervention to further assess safety and tolerance of anaesthesia of patients with limited respiratory reserve being assessed for further complex redo lung resection surgery. Further, this test was a risk stratification tool that allowed informed decisions to be made by the patient about therapeutic options for treating their lung cancer. The prognostic value of traditional physiological parameters in patients with chronic obstructive pulmonary disease who have undergone previous lung resection surgery is uncertain. The intraoperative oxygen challenge test is another risk stratification tool to assist clinicians in assessment of safety and tolerance of anaesthesia for patients being considered for lung resection.

Pulmonary diffusion capacity predicts major complications after esophagectomy for patients with esophageal cancer.

A reduced forced expiratory volume in one second (FEV1) is a well-recognized risk factor for complications after esophagectomy. Lung diffusing capacity for carbon monoxide (DLCO) is not routinely integrated in the risk assessment of esophagectomy. The aim of this study is to evaluate the association of preoperative pulmonary function tests with major postoperative complications after esophagectomy for cancer. In order to achieve this aim, 459 patients with newly diagnosed esophageal cancer who underwent elective transthoracic (n = 352) or transhiatal (n = 107) surgical resection of the esophagus with cervical anastomosis between 2003 and 2015 were analyzed. Multivariable logistic regression analysis was performed to assess the association of preoperative pulmonary function tests (expressed as % of predicted) with major complications after esophagectomy, adjusted for previously identified predictors. Major complications were defined as Clavien-Dindo grade IIIb or higher. Of the 459 included patients, 114 (24.8%) developed major complications. In univariable analysis FEV1, forced vital capacity (FVC), vital capacity (VC), and DLCO were associated with major complications. After adjusting each pulmonary function test for age, American Society of Anesthesiologists (ASA) score, cardiac comorbidity, diabetes mellitus, peripheral vascular disease, and surgical approach, FVC (OR: 1.24 per 10% decrease; 95% CI: 1.06-1.45; P = 0.004), VC (OR: 1.19 per 10% decrease; 95% CI: 1.02-1.39; P = 0.025) and DLCO (OR: 1.16 per 10% decrease; 95%CI: 1.02-1.33; P = 0.025) remained predictive factors for major surgical complications. In multivariable analysis in which all pulmonary functions tests were combined, DLCO was the strongest predictor of major complications (OR: 1.14 per 10% increase; 95% CI: 1.01-1.30; P = 0.046). The ideal cut-off for DLCO% of predicted was determined at <84% (OR: 1.97; 95% CI: 1.28-3.03; P = 0.002). These data indicate that DLCO is an independent predictor of major complications after esophagectomy for cancer. This pulmonary function test deserves greater consideration in prediction research of major complications after esophagectomy.

Reduction of cortical oxygenation in chronic kidney disease: evidence obtained with a new analysis method of blood oxygenation level-dependent magnetic resonance imaging.

BACKGROUND: Determinations of renal oxygenation by blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) in chronic kidney disease (CKD) patients have given heterogeneous results, possibly due to the lack of a reproducible method to analyse BOLD-MRI. It therefore remains uncertain whether patients with CKD have a reduced renal tissue oxygenation. We developed a new method to analyse BOLD-MRI signals and applied it to CKD patients and controls. METHODS: MRI was performed under standardized conditions before and 15 min after IV furosemide in 104 CKD patients, 61 hypertensives and 42 controls. MR images were analysed with the new twelve-layer concentric objects method (TLCO) that divides renal parenchyma in 12 layers of equal thickness. The mean R2* value of each layer was reported, along with the change in R2* between successive layers, as measured by the slope steepness of the relevant curve. RESULTS: Inter-observer variability was 2.3 ± 0.9%, 1.9 ± 0.8% and 3.0 ± 2.3% in, respectively, controls, moderate and severe CKD. The mean R2* of the outer (more cortical) layers was significantly higher in CKD, suggesting lower cortical oxygenation as compared with controls. In CKD patients, the response to furosemide was blunted in the inner (more medullary) layers, and the R2* slope was flatter. In multivariable regression analysis, the R2* slope correlated positively with estimated glomerular filtration rate (eGFR) in patients with an eGFR <90 mL/min/1.73 m2 (P < 0.001). CONCLUSIONS: Using the new TLCO method, we confirm the hypothesis that renal cortical oxygenation is reduced in CKD in humans, and that the level of cortical oxygenation correlates with CKD severity.

Blood Oxygenation Level-Dependent MRI to Assess Renal Oxygenation in Renal Diseases: Progresses and Challenges.

BOLD-MRI (blood oxygenation-level dependent magnetic resonance imaging) allows non-invasive measurement of renal tissue oxygenation in humans, without the need for contrast products. BOLD-MRI uses the fact that magnetic properties of hemoglobin depend of its oxygenated state:: the higher local deoxyhemoglobin, the higher the so called apparent relaxation rate R2* (sec-1), and the lower local tissue oxygen content. Several factors other than deoxyhemoglobin (such as hydration status, dietary sodium intake, and susceptibility effects) influence the BOLD signal, and need to be taken into account when interpreting results. The last 5 years have witnessed important improvements in the standardization of these factors, and the appearance of new, highly reproducible analysis techniques of BOLD-images, that are reviewed in this article. Using these new BOLD-MRI analysis techniques, it has recently been shown that persons suffering from chronic kidney diseases (CKD) have lower cortical oxygenation than normotensive controls, thus confirming the chronic hypoxia hypothesis. The acute alterations in R2* after the administration of furosemide are smaller in CKD, and represent an estimate of the oxygen-dependent tubular transport of sodium. BOLD-MRI-alone or in combination with other functional MRI methods- can be used to monitor the renal effects of drugs, and is increasingly used in the preclinical setting. The near future will tell whether or not BOLD-MRI represents a new tool to predict renal function decline an adverse renal outcome.

Importancia de la corrección de la KCO informada computarizada en pacientes con volumen alveolar disminuído / Importance to adjust computerized informed KCO in patients with low alveolar volume

La disminución del factor de transferencia de monóxido de carbono (TLCO) y del Volumen Alveolar (VA) no es uniforme. Los informes de los equipos computadorizados entregan un valor de KCO que no toma en cuenta este detalle.Objetivo: Realizar el cálculo de KCO a través de la corrección de Stam (J Apply Physiol 1994) y compararlas con las informadas por el software de un equipo de laboratorio pulmonar computadorizado reconocido (Collins).Material y Método: Fueron incluídos pacientes consecutivos derivados al Laboratorio Pulmonar de la Unidad para realizar una prueba de TLCO por enfermedad intersticial pulmonar entre Enero y Junio de 2008. Se realizaron las pruebas según recomendacionesATS/ERS por el método de respiración única y con el método de toma de muestra de Ogilvie. Se analizó la KCO según lo informa el software del equipo Collins Plus/SQL System (1995Warren Collins), y luego se lo recalculó corregida según el cálculo de Stam (J Apply Physiol 1994). Se incluyó en este análisis si tenían <80% del volumen alveolar predicho. Resultados: Fueron evaluados 15 pacientes (media edad: 57.5 ñ 12.9 años, sexo femenino 66.7%) con enfermedad intersticial.La media de VA fue 3.5ñ0.8 L(64.3ñ11.6%). La media de KCO informada a través del software fue 4.2ñ 1.3ml/min/mmHg/L. La media de KCO corregida fue 3.7 ñ 1.2ml/min/mmHg/L (Δ 11.8ñ3.8, rango: 6.8%-21.1%). Se observó una relación lineal y negativa entre el %VA y el delta de KCO corregida/informada (r2= -0.99). La elección de diferentes tablas de valores normales de VA altera hasta 12% el valor de la misma, pero la KCO corregida se altera en grado mínimo (3%). Conclusiones: Cuando el VA está disminuído, se debe realizar la corrección del informe computadorizado de la KCO, porque se observa una diferencia promedio del 12%, sobreestimando la real KCO del paciente. Otros factores, como la tabla de valores predictivos de VA, influencia muy poco la corrección de KCO. (AU)

The decrease of the Transfer Factor of the Lung for Carbon Monoxide (TLCO) and the Alveolar Volume (VA) is not uniform. Software of lung computed machine informs the carbon monoxide transfer coefficient TLCO/VA (KCO) by calculating the ratio without adjusting for that assumption. Objectives: To calculate KCO using a correction by the Stam´s equation (J Apply Physiol1994), to compare the corrected KCO with the result informed by the software of Collins lung laboratory equipment, and to evaluate the impact of using different predictive tables of VA in the estimates of KCO. Materials: Consecutive patients with intersticial lung disease who attended the LungLaboratory to perform the TLCO between January and June 2008 were included in the study. TLCO was performed according to ATS/ERS recommendations by the single-breathand Ogilvie methods. KCO was calculated by the software of Collins Plus/SQL System (1995 Warren Collins), and then recalculated by Stam´s equation. Only patients withless than 80% of VA predictive value were included. Results: 15 patients with interstitial lung disease were evaluated (age: 57.53 ñ 12.93 years old, female: 66.66%). The mean VA was 3.55 ñ0.83 L (64.33 ñ11.56%) and the mean KCO informed by software was 4.17 ñ1.31 ml/min/mmHg/L. The corrected KCO was 3.76 ñ1.33 ml/min/mmHg/L(Δ 11.84 ñ3.84, range: 6.82%-21.1%). It was observed a negative and lineal relation between %VA and Δ KCO corrected/informed (R2= -0.99). The election of different tables of VA normal values distorts up to12% the individualvalues, but the corrected KCO is little modified (3%). Conclusion: When the VA is reduced, the correction of the KCO must be performed, to avoid on average a 12% overestimate. Other factors such as the election of VA predictive tables have little influence on the KCO correction. (AU)

Importancia de la corrección de la KCO informada computarizada en pacientes con volumen alveolar disminuído / Importance to adjust computerized informed KCO in patients with low alveolar volume

La disminución del factor de transferencia de monóxido de carbono (TLCO) y del Volumen Alveolar (VA) no es uniforme. Los informes de los equipos computadorizados entregan un valor de KCO que no toma en cuenta este detalle.Objetivo: Realizar el cálculo de KCO a través de la corrección de Stam (J Apply Physiol 1994) y compararlas con las informadas por el software de un equipo de laboratorio pulmonar computadorizado reconocido (Collins).Material y Método: Fueron incluídos pacientes consecutivos derivados al Laboratorio Pulmonar de la Unidad para realizar una prueba de TLCO por enfermedad intersticial pulmonar entre Enero y Junio de 2008. Se realizaron las pruebas según recomendacionesATS/ERS por el método de respiración única y con el método de toma de muestra de Ogilvie. Se analizó la KCO según lo informa el software del equipo Collins Plus/SQL System (1995Warren Collins), y luego se lo recalculó corregida según el cálculo de Stam (J Apply Physiol 1994). Se incluyó en este análisis si tenían <80% del volumen alveolar predicho. Resultados: Fueron evaluados 15 pacientes (media edad: 57.5 ± 12.9 años, sexo femenino 66.7%) con enfermedad intersticial.La media de VA fue 3.5±0.8 L(64.3±11.6%). La media de KCO informada a través del software fue 4.2± 1.3ml/min/mmHg/L. La media de KCO corregida fue 3.7 ± 1.2ml/min/mmHg/L (Δ 11.8±3.8, rango: 6.8%-21.1%). Se observó una relación lineal y negativa entre el %VA y el delta de KCO corregida/informada (r2= -0.99). La elección de diferentes tablas de valores normales de VA altera hasta 12% el valor de la misma, pero la KCO corregida se altera en grado mínimo (3%). Conclusiones: Cuando el VA está disminuído, se debe realizar la corrección del informe computadorizado de la KCO, porque se observa una diferencia promedio del 12%, sobreestimando la real KCO del paciente. Otros factores, como la tabla de valores predictivos de VA, influencia muy poco la corrección de KCO.

The decrease of the Transfer Factor of the Lung for Carbon Monoxide (TLCO) and the Alveolar Volume (VA) is not uniform. Software of lung computed machine informs the carbon monoxide transfer coefficient TLCO/VA (KCO) by calculating the ratio without adjusting for that assumption. Objectives: To calculate KCO using a correction by the Stam´s equation (J Apply Physiol1994), to compare the corrected KCO with the result informed by the software of Collins lung laboratory equipment, and to evaluate the impact of using different predictive tables of VA in the estimates of KCO. Materials: Consecutive patients with intersticial lung disease who attended the LungLaboratory to perform the TLCO between January and June 2008 were included in the study. TLCO was performed according to ATS/ERS recommendations by the single-breathand Ogilvie methods. KCO was calculated by the software of Collins Plus/SQL System (1995 Warren Collins), and then recalculated by Stam´s equation. Only patients withless than 80% of VA predictive value were included. Results: 15 patients with interstitial lung disease were evaluated (age: 57.53 ± 12.93 years old, female: 66.66%). The mean VA was 3.55 ±0.83 L (64.33 ±11.56%) and the mean KCO informed by software was 4.17 ±1.31 ml/min/mmHg/L. The corrected KCO was 3.76 ±1.33 ml/min/mmHg/L(Δ 11.84 ±3.84, range: 6.82%-21.1%). It was observed a negative and lineal relation between %VA and Δ KCO corrected/informed (R2= -0.99). The election of different tables of VA normal values distorts up to12% the individualvalues, but the corrected KCO is little modified (3%). Conclusion: When the VA is reduced, the correction of the KCO must be performed, to avoid on average a 12% overestimate. Other factors such as the election of VA predictive tables have little influence on the KCO correction.