Effects of Supplemental Oxygen on Cardiovascular and Respiratory Interactions by Extended Partial Directed Coherence in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and restrictive disease characterized by fibrosis and inflammatory changes in lung tissue producing a reduction in diffusion capacity and leading to exertional chronic arterial hypoxemia and dyspnea. Furthermore, clinically, supplemental oxygen (SupplO2) has been prescribed to IPF patients to improve symptoms. However, the evidence about the benefits or disadvantages of oxygen supplementation is not conclusive. In addition, the impact of SupplO2 on the autonomic nervous system (ANS) regulation in respiratory diseases needs to be evaluated. In this study the interactions between cardiovascular and respiratory systems in IPF patients, during ambient air (AA) and SupplO2 breathing, are compared to those from a matched healthy group. Interactions were estimated by time series of successive beat-to-beat intervals (BBI), respiratory amplitude (RESP) at BBI onset, arterial systolic (SYS) and diastolic (DIA) blood pressures. The paper explores the Granger causality (GC) between systems in the frequency domain by the extended partial directed coherence (ePDC), considering instantaneous effects. Also, traditional linear and nonlinear markers as power in low (LF) and high frequency (HF) bands, symbolic dynamic indices as well as arterial baroreflex, were calculated. The results showed that for IPF during AA phase: 1) mean BBI and power of BBI-HF band, as well as mean respiratory frequency were significantly lower (p < 0.05) and higher (p < 0.001), respectively, indicating a strong sympathetic influence, and 2) the RESP → SYS interaction was characterized by Mayer waves and diminished RESP → BBI, i.e., decreased respiratory sinus arrhythmia. In contrast, during short-term SupplO2 phase: 1) oxygen might produce a negative influence on the systolic blood pressure variability, 2) the arterial baroreflex reduced significantly (p < 0.01) and 3) reduction of RSA reflected by RESP → BBI with simultaneous increase of Traube-Hering waves in RESP → SYS (p < 0.001), reflected increased sympathetic modulation to the vessels. The results gathered in this study may be helpful in the management of the administration of SupplO2.

[Overview of the interstitial lung disease in the Southeast of Mexico]. / Panorama de la enfermedad pulmonar intersticial en el sureste de México.

Background: Interstitial lung disease (ILD) corresponds to a heterogeneous group of pathologies that differ in etiology with common clinical and radiological manifestations. In Latin America and Mexico, reports are scarce and the need for studies to understand the scenario is emphasized. Objective: To analyze a multidimensional profile in patients with interstitial lung disease in Yucatan. Method: This is an observational, prospective, analytic, descriptive study including consecutive patients diagnosed with ILD over a 4-year period. Demographic and clinical data, lung function tests, chest imaging, serum immunological profile, and echocardiographic findings were recorded. Differences between subgroups were analyzed performing a one-way analysis of variance (ANOVA). Results: 110 patients were included. The median age was 60 years and women were most affected. The main cause of ILD was related with connective tissue diseases (CTD). A group subanalysis revealed that Idiopathic pulmonary fibrosis (IPF) was common in males with a history of smoking and an imaging pattern of usual interstitial pneumonia. Lung function tests showed a moderate-to-severe pulmonary restriction (FVC 55%p) and mild hypoxemia (PaO2 79mmHg). Positive antinuclear antibodies are less likely in cases with IPF (20 vs. 65%; p = 0.006). Conclusion: In Southeastern Mexico, ILD occurs in women in their seventh decade of life; the most common cause is related with CTD. Our results support that ILD has a heterogeneous expression and is relevant the need for subsequent studies characterizing each ILD.

Introducción: La enfermedad pulmonar intersticial (EPI) corresponde a un grupo heterogéneo de patologías que difieren en su etiología pero tienen manifestaciones clínicas y radiológicas comunes. En Latinoamérica y México los reportes son escasos, enfatizando la necesidad de estudios que permitan conocer su escenario clínico-epidemiológico. Objetivo: Realizar un análisis multidimensional y contrastado de la EPI en la población de la Península de Yucatán. Método: Estudio observacional, prospectivo, analítico y descriptivo, que incluye la totalidad de pacientes diagnosticados de EPI en un período de 4 años. Se registraron datos demográficos y clínicos, pruebas de función pulmonar, imagenología del tórax, perfil inmunológico y ecocardiografía transtorácica. Se analizaron las diferencias según la etiología mediante análisis de la varianza de una sola vía (ANOVA). Resultados: Se incluyeron 110 pacientes con una mediana de edad de 60 años y predominio del sexo femenino. La causa principal de la EPI fue relacionada con enfermedad del tejido conectivo. El subanálisis de grupos mostró que la fibrosis pulmonar idiopática (FPI) es frecuente en los varones con antecedente de tabaquismo y patrón tomográfico de neumonía intersticial usual. Las pruebas de función pulmonar demostraron restricción pulmonar moderadamente grave (FVC 55%p) e hipoxemia leve (PaO2 79 mmHg). La positividad de anticuerpos antinucleares ocurre en menor proporción en la FPI (20 vs. 65%, p = 0.006). Conclusiones: En el sureste de México, la EPI ocurre en mujeres de la séptima década de la vida y se relaciona con enfermedad del tejido conectivo. Nuestros resultados respaldan que la EPI tiene expresión heterogénea y se requieren estudios subsecuentes sobre cada tipo de enfermedad.

Hemodynamic response to low-flow acute supplemental oxygen in idiopathic pulmonary fibrosis and elderly healthy subjects.

BACKGROUND: Hemodynamic response to supplemental oxygen in idiopathic pulmonary fibrosis (IPF) is still not well known. OBJECTIVE: To determine and compare the effect of low-flow acute supplemental oxygen on the hemodynamics of IPF patients and matched healthy subjects. METHODS: Descriptive and comparative study in 20 IPF-patients and 19 Control-subjects, (60-80 years old) breathing ambient air followed by acute nasal low-flow (3 L/min) supplemental oxygen. Non-invasive methods were used during the supine position to evaluate oxygen saturation, heart rate, stroke volume index, cardiac output index, total peripheral resistance and arterial blood pressure. RESULTS: Breathing ambient air, IPF (vs. Control) presented lower values in stroke volume index (38.7 [29.4-43.2] vs. 45.4 [38.4-50.9] mL•kg-1•m2; p=0.009) and cardiac output index (2.484 [2.268 - 2.946] vs. 2.857 [2.628 - 3.054] L•min-1•m-2; p=0.028), with higher total peripheral resistance (1644 [1559-2076] vs. 1505 [1366-1784] dyne•s•cm-5; p=0.017). During supplemental oxygen (vs. ambient air), both groups increased oxygen saturation above 94% (p<0.001) while heart rate decreased about 6 to 8% (p<0.001); stroke volume index increased around 7% in the Control-group (p=0.004) but only 1% in the IPF-group (p=0.017). In addition, IPF showed increments in total peripheral resistance (1644 [1559-2076] vs. 1706 [1554-2278] dyne•s•cm-5; p=0.017) with subsequent decrements in cardiac output index (2.484 [2.268 - 2.946] vs. 2.362 [2.139 - 2.664] L•min-1•m-2; p<0.001). CONCLUSION: Low-flow acute supplemental oxygen in IPF causes a meaningful decrement in cardiac output due to greater reduction in heart rate and increment in total peripheral resistance than matched healthy subjects. Knowing the hemodynamic profile of IPF patients may be helpful in determining their management with supplemental oxygen.

An Open-label Study With Pirfenidone on Chronic Hypersensitivity Pneumonitis / Estudio abierto con pirfenidona en neumonitis por hipersensibilidad crónica

BACKGROUND: Chronic hypersensitivity pneumonitis (cHP) represents a severe lung disease often evolving to fibrosis with the subsequent destruction of the lung parenchyma. There are no approved therapies with confirmed efficacy to deal with this disease. METHODS: We performed an open-label, proof of concept study, to evaluate the efficacy and safety of pirfenidone added to immunosuppressive drugs on the treatment of cHP. We included 22 patients assigned to two groups: Group 1, nine patients that received prednisone plus azathioprine and Group 2, thirteen patients, received prednisone plus azathioprine and pirfenidone (ClinicalTrials.gov identifier NCT02496182). There were no significant imbalances in clinically relevant baseline characteristics between two study groups. RESULTS: After 1 year of treatment, inclusion of pirfenidone was not associated with improved forced vital capacity (primary end-point). A not significant tendency to show higher improvement of diffusion capacity of the lung for carbon monoxide (DLCO) was observed in the group receiving pirfenidone (p = 0.06). Likewise, a significant improvement in the total score on the SGRQ was found in the group 2 (p = 0.02) without differences in other two questionnaires related to quality of life (ATAQ-IPF and EQ-5D-3L). HRCT showed a decrease of the ground glass attenuation without changes in the fibrotic lesions and without differences between both groups. CONCLUSIONS: These findings suggest that the addition of pirfenidone to the anti-inflammatory treatment in patients with chronic HP may improve the outcome with acceptable safety profile. However, prospective randomized double-blind, placebo-controlled trials in largest cohorts are needed to validate its efficacy

ANTECEDENTES: La neumonitis por hipersensibilidad crónica es una enfermedad pulmonar grave que con frecuencia evoluciona hacia fibrosis, con la ulterior destrucción del parénquima pulmonar. No existen tratamientos aprobados con eficacia confirmada para el manejo de esta enfermedad. MÉTODOS: Llevamos a cabo un estudio preliminar de eficacia, abierto, para evaluar la eficacia y la seguridad de la pirfenidona sumada a los fármacos inmunosupresores en el tratamiento de la neumonitis por hipersensibilidad crónica. Se incluyeron 22 pacientes, que se asignaron a dos grupos: grupo 1, 9 pacientes que recibieron prednisona y azatioprina; y grupo 2, 13 pacientes que recibieron prednisona, azatioprina y pirfenidona (identificador NCT02496182 en ClinicalTrials.gov). No se observaron alteraciones significativas en las características clínicamente relevantes iniciales entre ambos grupos. RESULTADOS: Tras un año de tratamiento, la inclusión de la pirfenidona no se asoció con una mejora de la capacidad vital forzada (objetivo principal). Se observó una tendencia no significativa a mostrar una mayor mejora en la capacidad de difusión de monóxido de carbono (DLCO) por el pulmón en el grupo que recibió pirfenidona (p = 0,06). Asimismo, se encontró una mejora significativa en la puntuación total del cuestionario SGRQ en el grupo 2 (p = 0,02) sin encontrarse diferencias en los otros dos cuestionarios relacionados con la calidad de vida de los pacientes (ATAQ-IPF y EQ-5D-3L). La TAC de alta resolución mostró una disminución de la atenuación en «vidrio deslustrado», sin cambios en las fibrosis y sin diferencias entre ambos grupos. CONCLUSIONES: Estos hallazgos sugieren que añadir pirfenidona al tratamiento antiinflamatorio en pacientes con neumonitis por hipersensibilidad crónica podría mejorar el pronóstico con un perfil de seguridad aceptable. Sin embargo, se necesitan ensayos prospectivos aleatorizados doble ciego y controlados con placebo para validar esta eficacia

An Open-label Study With Pirfenidone on Chronic Hypersensitivity Pneumonitis.

BACKGROUND: Chronic hypersensitivity pneumonitis (cHP) represents a severe lung disease often evolving to fibrosis with the subsequent destruction of the lung parenchyma. There are no approved therapies with confirmed efficacy to deal with this disease. METHODS: We performed an open-label, proof of concept study, to evaluate the efficacy and safety of pirfenidone added to immunosuppressive drugs on the treatment of cHP. We included 22 patients assigned to two groups: Group 1, nine patients that received prednisone plus azathioprine and Group 2, thirteen patients, received prednisone plus azathioprine and pirfenidone (ClinicalTrials.gov identifier NCT02496182). There were no significant imbalances in clinically relevant baseline characteristics between two study groups. RESULTS: After 1 year of treatment, inclusion of pirfenidone was not associated with improved forced vital capacity (primary end-point). A not significant tendency to show higher improvement of diffusion capacity of the lung for carbon monoxide (DLCO) was observed in the group receiving pirfenidone (p=0.06). Likewise, a significant improvement in the total score on the SGRQ was found in the group 2 (p=0.02) without differences in other two questionnaires related to quality of life (ATAQ-IPF and EQ-5D-3L). HRCT showed a decrease of the ground glass attenuation without changes in the fibrotic lesions and without differences between both groups. CONCLUSIONS: These findings suggest that the addition of pirfenidone to the anti-inflammatory treatment in patients with chronic HP may improve the outcome with acceptable safety profile. However, prospective randomized double-blind, placebo-controlled trials in largest cohorts are needed to validate its efficacy.

A Smartphone-Based System for Automated Bedside Detection of Crackle Sounds in Diffuse Interstitial Pneumonia Patients.

In this work, we present a mobile health system for the automated detection of crackle sounds comprised by an acoustical sensor, a smartphone device, and a mobile application (app) implemented in Android. Although pulmonary auscultation with traditional stethoscopes had been used for decades, it has limitations for detecting discontinuous adventitious respiratory sounds (crackles) that commonly occur in respiratory diseases. The proposed app allows the physician to record, store, reproduce, and analyze respiratory sounds directly on the smartphone. Furthermore, the algorithm for crackle detection was based on a time-varying autoregressive modeling. The performance of the automated detector was analyzed using: (1) synthetic fine and coarse crackle sounds randomly inserted to the basal respiratory sounds acquired from healthy subjects with different signal to noise ratios, and (2) real bedside acquired respiratory sounds from patients with interstitial diffuse pneumonia. In simulated scenarios, for fine crackles, an accuracy ranging from 84.86% to 89.16%, a sensitivity ranging from 93.45% to 97.65%, and a specificity ranging from 99.82% to 99.84% were found. The detection of coarse crackles was found to be a more challenging task in the simulated scenarios. In the case of real data, the results show the feasibility of using the developed mobile health system in clinical no controlled environment to help the expert in evaluating the pulmonary state of a subject.

A multichannel acoustic approach to define a pulmonary pathology as combined pulmonary fibrosis and emphysema syndrome.

Interstitial lung diseases (ILDs) have been increasing their relevance in loss of lives according to a recent world wide medical information. Idiopathic pulmonary fibrosis (IPF) and combined pulmonary fibrosis and emphysema syndrome (CPFES) belong to ILD class with the latter having a limited survival prognosis. In clinical environment high resolution computed tomography (HRCT) is used to detect CPFE; however, there is still controversy about the amount of emphysema observed in HRCT to declare CPFES. Consequently, to help in the diagnosis of CPFES to develop an alternative technique seems to be attractive. In this study, we propose a multichannel acoustic approach to discriminate between IPF and CPFES parameterizing the multichannel lung sounds information linearly and classifying it by neural networks (NN). The NN performance using different features provided values above 90% in the validation phase. Furthermore, to test the trained NN, the proposed approach was applied on new data from five patients 3 diagnosed by experts as CPFES and 2 with IPF. The univariate autoregressive model obtained the best classification followed by the feature vector formed by the percentile frequencies augmented by the total power of the acoustic information. Results indicate that multichannel acoustic analysis is promising to discern between these two ILDs.

Small airway dysfunction in chronic hypersensitivity pneumonitis.

BACKGROUND AND OBJECTIVE: Lung biopsies from patients with hypersensitivity pneumonitis (HP) have demonstrated small airway (SA) involvement, but there is no information concerning SA function in HP, and it is unknown whether pharmacological treatment could modify its function. SA function in patients with chronic HP using ultrasonic pneumography (UPG) and impulse oscillometry (IOS) was explored. We also compared initial results with those obtained after 4 weeks of standardized treatment with azathioprine and prednisone. METHODS: The study group consisted of adults with recent diagnoses of HP. All patients completed UPG, IOS, spirometry, body plethysmography, single-breath carbon monoxide diffusing capacity (DLCO ) and the 6-min walk test (6MWT). The fraction of exhaled nitric oxide (FENO ) was obtained to assess eosinophilic airway inflammation. Measurements were taken at diagnosis and after 4 weeks of treatment. RESULTS: A total of 20 consecutive patients (16 women) with chronic HP participated in the study. Median age was 50 years (interquartile range (IQR): 42-54). At diagnosis, the UPG phase 3 slope was abnormally high, consistent with maldistribution of ventilation. For IOS, all patients had low reactance at 5 Hz (X5) and elevated reactance area (AX) reflecting low compliance, and only eight (40%) patients had elevated R5 (resistance at 5 Hz (total)) and R5-20 (resistance at 5 Hz-resistance at 20 Hz (peripheral)) attributed to SA resistance. In contrast, FENO parameters were within normal limits. After treatment, forced vital capacity (FVC), the 6-min walk distance and the distribution of ventilation showed significant improvement, although DLCO did not. CONCLUSION: Patients with chronic HP have SA abnormalities that are partially revealed by the UPG and IOS tests. Lung volumes, but not gas exchange, improved after treatment with azathioprine and prednisone.

Sarcoidosis: a single hospital-based study in a 24-year period.

BACKGROUND: Clinical presentation of sarcoidosis varies according to race and geographical area. We describe the clinical spectrum and outcome of sarcoidosis in Mexican patients compared with other populations. METHODS: We reviewed the medical charts of 21 patients with sarcoidosis seen at a referral hospital in 1989-2012; organ involvement was assessed using the ACCESS instrument. We compared our results with the ACCESS and Latin American studies. We used descriptive statistics and reported odd ratios with 95% CI. RESULTS AND CONCLUSION: Fifty-two percent were women; median age was 31 years; median time to diagnosis, 5.5 months. Frequency of organ involvement was: constitutional symptoms 62%, lungs 66.6%, skin 42.8%, bone marrow 23.4%, lymph node 19%, liver 19%, and eye 19%. After one year of follow-up, 47.5% of patients were asymptomatic without treatment, 38% asymptomatic on treatment, and 14.2% symptomatic on treatment. In our patients, pulmonary involvement was lower (66.6 vs. 94.9%; p = 0.001) and cutaneous (42.8 vs. 15.8%; p = 0.003) and bone marrow (23.4 vs. 4.7%; p = 0.001) were higher than in the ACCESS cohort. Data regarding Latin American populations was scarce. The clinical spectrum of sarcoidosis in our population differed from other studies, with a higher frequency of cutaneous sarcoidosis and less pulmonary involvement.

Prevalencia de iiabetes mellitus en pacientes con fibrosis pulmonar idiopática

La prevalencia de diabetes mellitus tipo 2 (DM2) en México es del 10%. Objetivo: Determinar la prevalencia de DM2 en pacientes con fibrosis pulmonar idiopática (FPI), neumonitis por hipersensibilidad (NH) y cáncer pulmonar (CP) en la ciudad de México. Casos: 136 pacientes con FPI; controles: 53 pacientes con NH y 263 con CP. El diagnóstico de DM2 se basó en dos glicemias en ayuno por arriba de 126mg/dL. Resultados: Veintinueve pacientes (21.3%) con FPI, 4 (7.5%) con NH y 25 (9.5%) con CP, tuvieron DM2, con una prevalencia significativamente mayor en la FPI en relación con la NH razón de momios 3.3 (intervalo de confianza 95% 1.1-9.6) p < 0.01 y con CP [razón de momios 2.5 (intervalo de confianza 95% 1.4-4.6) p<0.01]. No se observaron diferencias estadísticamente significativas en relación con el género, obesidad y nivel socioeconómico Conclusión: La prevalencia de DM2 en FPI, es mayor que en los controles y en la población general. La obesidad, género y nivel socioeconómico no influyeron en la DM2.

Prevalence of type 2 diabetes mellitus (DM2) in Mexico is 10%. Objective: to describe the prevalence of DM2 in Idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP) and lung cancer patients (LC) in Mexico City. Cases: 136 patients with IPF. The control groups were 53 hypersensitivity pneumonitis patients (HP) and 263 lung cancer patients (LC). DM2 was determined by two preprandial serum glucose levels higher than 126 mg/dL. Results: 29 (21.3%) IPF patients, 4 (7.5%) HP patients and 25 (9.5%) LC patients had DM2, revealing a significantly higher prevalence of DM2 in IPF/HP [odds ratio 3.3 (95% CI 1.1-9.6) p<0.01] and IPF/LC [odds ratio 2.5 (95% CI 1.4-4.6) p<0.01]. No differences were seen when IPF patients were divided by gender, obesity and economic level. Conclusions: These results suggest that there is a higher prevalence of DM2 in IPF patients in comparison with HP, LC patients and the general population in Mexico City.

La importancia de la gammagrafía pulmonar en cirugía de resección pulmonar: caso clínico / Importance of lung gammagraphy in the resection lung surgery. a clinical case

La presentación de este caso clínico tiene por objeto resaltar la utilidad de la medicina nuclear en el protocolo de valoración prequirúrgica de resección de tejido pulmonar. Se trató de una paciente con una enfermedad pulmonar obstructiva crónica asociada a neoplasia pulmonar (tumor carcinoide), que evolucionó sin un diagnóstico preciso durante algunos años. Una vez realizado el diagnóstico de la enfermedad, se encontró con una alteración funcional importante que contraindicaba una resección pulmonar amplia. Sin embargo, la gammagrafía pulmonar ventilatoria-perfusoria permitió una adecuada conducta quirúrgica

La conducta de un grupo de médicos mexicanos ante el diagnóstico y tratamiento del asma / The behavior of a group of mexican physicians on the diagnosis and treatment of asthma

En la práctica diaria es común la atención de enfermos asmáticos en los diferentes niveles de atención a la salud. Existen criterios uniformes para la evaluación tratamiento de estos pacientes. El motivo del presente estudio fue conocer si estos criterios son utilizados por un grupo de médicos mexicanos. Se aplicaron encuestas a 215 médicos de cuatro ciudades del país (México D.F., Veracruz, Zihuatanejo y Tijuana): 154 médicos generales, 36 neumólogos y 25 pediatras. El cuestionario comprendió 21 preguntas, 6 dirigidas a conocer aspectos diagnósticos y 15 a conductas terapéuticas. Los resultados muestran un mismo criterio entre los médicos especialistas en los reactivos relacionados con aspectos diagnósticos y diferente a los médicos generales. En el aspecto terapéutico se encontró que en 8 preguntas el criterio fue similar para los 3 grupos; en 3, el grupo de neumólogos difiere de los otros 2 grupos; en uno el grupo de pediatras y en 3, los médicos generales. Se encuentra una importante discrepancia entre los grupos de médicos encuestados, en relación con la evaluación de la severidad y la conducta terapéutica de esta enfermedad. Por otra parte, también es evidente que muchas de las conductas clínicas y terapéuticas vertidas por los clínicos en el cuestionario no son las que se consideran correctas de acuerdo a lo establecido actualmente. Finalmente, nuestros resultados sugieren que es necesario establecer programas específicos de educación en los diferentes niveles de atención a la salud