Survival and Lung Function Changes in Hypersensitivity Pneumonitis According to Radiological Phenotypes Compared With Idiopathic Pulmonary Fibrosis.

INTRODUCTION: The main objective of this study was to estimate survival and changes in lung function in patients with chronic hypersensitivity pneumonitis (HP), both fibrotic (f-HP) and nonfibrotic (nf-HP), and to compare them with those in patients with idiopathic pulmonary fibrosis (IPF). METHODS: HP was diagnosed based on antigen exposure, HRCT (high-resolution CT scan), BAL (bronchoalveolar lavage), and histology. According to HRCT, HP was classified into fibrotic and non-fibrotic phenotypes. In most cases, IPF was diagnosed based on HRCT findings. RESULTS: We identified 84 patients: 46 with IPF, 18 with f-HP, and 20 with nf-HP. Five-year survival was 23.9% in IPF, 72% in f-HP, and 100% in nf-HP (p <0.0001). Honeycombing was associated with decreased survival in IPF (p <0.001) and in f-HP (p <0.0001). The mean loss of FVC (forced vital capacity) % pred. (percent predicted) was -18.3% in IPF (p =0.001), -4.8% in f-HP, and -6.0% in nf-HP. The mean change in DLCO (diffusion capacity for carbon monoxide) % pred. was -10.2% in IPF (p <0.002), -0.5% in f-HP, and +1.9% in nf-HP. The agreement between radiological phenotypes and histology in HP was 89.6%. CONCLUSIONS: We found shorter survival in IPF, followed by f-HP, and nf-HP. Over time, we did not find significant changes in FVC% pred. or DLCO% pred. in HP, while a significant decline in IPF was noted. In HP, we found strong agreement between radiological phenotypes and histology. Radiological signs suggestive of lung fibrosis in HP were reliable for the diagnosis of f-HP and seem to have intrinsic prognostic value.

Safety of inhaled nitric oxide withdrawal in severe chronic pulmonary hypertension.

Inhaled nitric oxide (iNO) is a potent and selective pulmonary vasodilator with a safety concern due to rebound pulmonary hypertension (PH) associated with its withdrawal. We report short-term pulsed iNO in patients with severe pulmonary arterial hypertension (PAH) and nonoperable chronic thromboembolic PH (nCTEPH). This is a retrospective analysis of 33 patients: 22 with PAH and 11 with nCTEPH. We assessed hemodynamic, echocardiographic, and other noninvasive variables to evaluate safety and efficacy of iNO. We performed an iNO withdrawal test during right heart catheterization and after 3 days of iNO treatment. iNO significantly improved all variables examined in 22 patients with PAH and 11 with nCTEPH. Two patterns of response were observed after sudden iNO withdrawal. Twenty-nine patients (88%) showed minimal hemodynamic, oxygenation and clinical changes. Four patients (12%) had a reduction in cardiac index ≥20% and PaO2 ≥ 5%, three patients did not show clinical deterioration, and one patient developed hemodynamic collapse that needed iNO administration. This retrospective study suggests that short-term iNO improves hemodynamics and clinical conditions in some patients with PAH an nCTPEH. However, pulsed iNO withdrawal PH rebound could be a serious concern in these patients. Given the lack of evidence, we do not recommend the use of pulsed iNO in the treatment of patients with chronic PH.

Prevalence of sensitization to Blomia tropicalis among young adults in a temperate climate.

BACKGROUND: There are no previous population-based studies assessing the prevalence of Blomia tropicalis (BT). This investigation analyzes the prevalence of sensitization to BT and its contribution to asthma and related diseases among young adults in the Canary Islands. MATERIAL AND METHODS: From a random sample of 9506 adults, aged between 20 and 44, who had previously answered a short respiratory questionnaire, a further 20% random sample was drawn. All participants filled in an extensive questionnaire, and they underwent spirometry and bronchial hyperresponsiveness (BHR) test and skin testing to several allergens as well as the determination of total IgE and specific IgE. RESULTS: The prevalence of positive skin tests to BT was 13.8% (95% confidence interval [CI] 10.6-17.9%) and that of BT-specific IgE 17.9% (95% CI 14.2-24.5%). Sensitization to BT (positive skin tests or positive specific IgE) was 20.9% (95% CI 16.9-25.5%). Most of the subjects sensitized to BT were also sensitized to Dermatophagoides pteronissimus; however, only 7% displayed monosensitization to BT. Among subjects who exhibited BHR, sensitization to BT reached 46.7% (95% CI 32.7-60.9%), among those with asthma 50% (95% CI 26.8-73.2%), in subjects with rhinitis 37.2% (95% CI 28.1-47.6%), and in those suffering from dermatitis 25.9% (95% CI 18.7-34.5%). A strong association of BT sensitization with BHR and asthma before and after 15 years was found. CONCLUSION: The prevalence of sensitization to BT among young adults in the Canary Islands is high, and it displays a close relationship with allergic respiratory diseases and dermatitis.

Greedy based convolutional neural network optimization for detecting apnea.

BACKGROUND AND OBJECTIVE: Sleep apnea is a common sleep disorder, usually diagnosed using an expensive, highly specialized, and inconvenient test called polysomnography. A single SpO2 sensor based on an automated classification system can be developed to simplify the apnea detection. The main objective of this work is to develop a classifier based on a convolution neural network with the capability of detecting apnea events from one dimensional SpO2 signal. However, to find an optimum convolution neural network structure is a daunting task is usually done by a trial-and-error method. To solve this problem, a method is proposed to save time and simplify the process of searching for an optimum convolution neural network structure. METHODS: Greedy based optimization is proposed to search for an optimized convolution neural network structure. Three different variants of greedy based optimization are proposed: the topology transfer, the weighted-topology transfer with rough estimation, and the weighted-topology transfer with fine tuning. The subject independent and the cross-database test are performed for the analysis. RESULTS: Considering the balance between the execution time and the performance, the weighted-topology transfer with rough estimation is the best. An accuracy of 88.49% for the HuGCDN2008 database and 95.14% for the Apnea-ECG database are obtained for apnea events detection per minute. Regarding the apnea patient detection, also referred to as global classification, an accuracy of 95.71% is achieved for the HuGCDN2008 database, and 100% is achieved for the AED database without removing any subjects from both databases. CONCLUSIONS: The proposed one-dimensional convolution neural network performs better in a similar situation than those presented in the literature. The greedy based methods, mainly the weighted-topology transfer with rough estimation, is an alternative method to extensive trial and error method.

Sleep apnea: Tracking effects of a first session of CPAP therapy by means of Granger causality.

Connectivity between physiological networks is an issue of particular importance for understanding the complex interaction brain-heart. In the present study, this interaction was analyzed in polysomnography recordings of 28 patients diagnosed with obstructive sleep apnea (OSA) and compared with a group of 10 control subjects. Electroencephalography and electrocardiography signals from these polysomnography time series were characterized employing Granger causality computation to measure the directed connectivity among five brain waves and three spectral subbands of heart rate variability. Polysomnography data from OSA patients were recorded before and during a first session of continuous positive air pressure (CPAP) therapy in a split-night study. Results showed that CPAP therapy allowed the recovery of inner brain connectivities, mainly in subsystems involving the theta wave. In addition, differences between control and OSA patients were established in connections that involve lower frequency ranges of heart rate variability. This information can be potentially useful in the initial diagnosis of OSA, and determine the role of cardiac activity in sleep dynamics based on the use of three subbands of heart rate variability.

Improving the understanding of sleep apnea characterization using Recurrence Quantification Analysis by defining overall acceptable values for the dimensionality of the system, the delay, and the distance threshold.

Our contribution focuses on the characterization of sleep apnea from a cardiac rate point of view, using Recurrence Quantification Analysis (RQA), based on a Heart Rate Variability (HRV) feature selection process. Three parameters are crucial in RQA: those related to the embedding process (dimension and delay) and the threshold distance. There are no overall accepted parameters for the study of HRV using RQA in sleep apnea. We focus on finding an overall acceptable combination, sweeping a range of values for each of them simultaneously. Together with the commonly used RQA measures, we include features related to recurrence times, and features originating in the complex network theory. To the best of our knowledge, no author has used them all for sleep apnea previously. The best performing feature subset is entered into a Linear Discriminant classifier. The best results in the "Apnea-ECG Physionet database" and the "HuGCDN2014 database" are, according to the area under the receiver operating characteristic curve, 0.93 (Accuracy: 86.33%) and 0.86 (Accuracy: 84.18%), respectively. Our system outperforms, using a relatively small set of features, previously existing studies in the context of sleep apnea. We conclude that working with dimensions around 7-8 and delays about 4-5, and using for the threshold distance the Fixed Amount of Nearest Neighbours (FAN) method with 5% of neighbours, yield the best results. Therefore, we would recommend these reference values for future work when applying RQA to the analysis of HRV in sleep apnea. We also conclude that, together with the commonly used vertical and diagonal RQA measures, there are newly used features that contribute valuable information for apnea minutes discrimination. Therefore, they are especially interesting for characterization purposes. Using two different databases supports that the conclusions reached are potentially generalizable, and are not limited by database variability.

Heart rate variability feature selection in the presence of sleep apnea: An expert system for the characterization and detection of the disorder.

We introduce a sleep apnea characterization and classification approach based on a Heart Rate Variability (HRV) feature selection process, thus focusing on the characterization of the underlying process from a cardiac rate point of view. Therefore, we introduce linear and nonlinear variables, namely Cepstrum Coefficients (CC), Filterbanks (Fbank) and Detrended Fluctuation Analysis (DFA). Logistic Regression, Linear Discriminant Analysis and Quadratic Discriminant Analysis were used for classification purposes. The experiments were carried out using two databases. We achieved a per-segment accuracy of 84.76% (sensitivity = 81.45%, specificity = 86.82%, AUC = 0.92) in the Apnea-ECG Physionet database, whereas in the HuGCDN2014 database, provided by the Dr. Negrín University Hospital (Las Palmas de Gran Canaria, Spain), the best results were: accuracy = 81.96%, sensitivity = 70.95%, specificity = 85.47%, AUC = 0.87. The former results were comparable or better than those obtained by other methods for the same database in the recent literature. We have concluded that the selected features that best characterize the underlying process are common to both databases. This supports the fact that the conclusions reached are potentially generalizable. The best results were obtained when the three kinds of features were jointly used. Another notable fact is the small number of features needed to describe the phenomenon. Results suggest that the two first Fbanks, the first CC and the first DFA coefficient are the variables that best describe the RR pattern in OSA and, therefore, are especially relevant to extract discriminative information for apnea screening purposes.

Hospital volume: operative morbidity, mortality and survival in thoracotomy for lung cancer. A Spanish multicenter study of 2994 cases.

INTRODUCTION: It has been hypothesized that medical procedures performed in high-volume units carry less risk and achieve a better outcome. OBJECTIVE: To determine the relationship between the number of interventions and the operative morbidity, mortality and long-term survival in the surgery of bronchogenic carcinoma (BC). PATIENTS AND METHOD: Prospective, multicenter Spanish study was conducted in 19 departments of thoracic surgery on 2994 patients operated on consecutively with the aim of curing BC. The thoracic surgery departments have been classified into three groups, according to the number of interventions performed per year: I (1-43 cases/year; centers=7; n=565; 18.9%), II (44-54 cases/year; centers=6; n=1044; 34.9%) and III (55 or more cases/year; centers=6; n=1385; 46.3%). RESULTS: When the three groups were compared, the frequency of complete surgery was found to be 84% for group I, 76% for group II and 83% for group III (p=0.001, for comparisons between groups I/II and II/III). The pathological stages were identical in the three groups. The overall morbidity and the mortality in all patients or above the age of 75 or in pneumonectomies were not different among the groups. When considering all the patients with prognostic information (n=2758), no differences were found regarding the 5-year survival among the groups. When only patients in postoperative stage I-II and complete resection were evaluated, excluding operative mortality (n=1128), 5-year survival was 0.58 for group I, 0.57 for group II and 0.50 for group III (p=0.06 between groups II and III; p=0.08 between groups I and III). CONCLUSIONS: No significant differences that do not favor the hypothesis that there is increased surgical risk and worse survival in centers having a lower volume were found in this Spanish multicenter study.

Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus: Prevalence and Predictors.

OBJECTIVE: Pulmonary arterial hypertension (PAH) prevalence has been reported to be between 0.5% and 17% in systemic lupus erythematosus (SLE). This study assessed PAH prevalence and predictors in an SLE cohort. METHODS: The Borg dyspnea scale, DLCO, N-terminal pro-brain natriuretic peptide (NT-proBNP), and Doppler echocardiographic (DE) were performed. An echocardiographic Doppler exercise test was conducted in selected patients. When DE systolic pulmonary arterial pressure was ≥ 45 mmHg or increased during exercise > 20 mmHg, a right heart catheterization was performed. Hemodynamic during exercise was measured if rest mean pulmonary arterial pressure was < 25 mmHg. RESULTS: Of the 203 patients with SLE, 152 were included. The mean age was 44.9 ± 12.3 years, and 94% were women. Three patients had known PAH. The algorithm diagnosed 1 patient with chronic thromboembolic pulmonary hypertension and 5 with exercise-induced pulmonary artery pressure increase (4 with occult left diastolic dysfunction). These patients had significantly more dyspnea, higher NT-proBNP, and lower DLCO. CONCLUSION: These data confirm the low prevalence of PAH in SLE. In our cohort, occult left ventricular diastolic dysfunction was a frequent diagnosis of unexplained dyspnea. Dyspnea, DLCO, and NT-proBNP could be predictors of pulmonary hypertension in patients with SLE.

Long-term pulmonary function after thoracic sympathectomy.

BACKGROUND: The purpose of this study was to evaluate the long-term and midterm effects of thoracic sympathectomy on pulmonary function and to assess the influence of the sympathetic nervous system on bronchomotor tone. METHODS: Thirty-seven consecutive patients were diagnosed with primary hyperhidrosis requiring thoracic sympathectomy and were included in this study. Spirometry and methacholine challenge testing were performed before and 3 months after surgery. To assess the long-term effects of the intervention, another spirometric study was performed 1 year later. RESULTS: Spirometry 3 months after surgery showed a significant decrease in the forced vital capacity (-5.2%), the forced expiratory volume in the first second (-6.1%), and the forced expiratory flow between 25% and 75% of vital capacity (-5.1%). Whereas methacholine challenge testing before surgery was positive in 3 subjects (2 of whom were asthmatic), it was positive in 6 patients after the procedure; differences were not statistically significant. After 12 months, forced vital capacity started recovering, and forced expiratory volume in the first second and forced expiratory flow rate 25% to 75% showed a sustained and significant reduction (-2.8% and -11.2%, respectively); however, patients remained asymptomatic. CONCLUSIONS: We conclude that thoracic sympathectomy generates a mild, although significant, impairment of the bronchomotor tone, with no clinical consequences. These results suggest that the sympathetic nervous system is involved in pulmonary bronchomotor tone.

Prevalence of chronic obstructive pulmonary disease in the Canary Islands.

INTRODUCTION: The prevalence of chronic obstructive pulmonary disease (COPD) varies significantly among the different geographical areas reported. In Spain, two epidemiological studies have shown a prevalence of 9-10% in the population aged over 40. However, neither of these studies included the Canary Islands, which are of interest due to their climatic conditions and high incidence of smoking. MATERIALS AND METHODS: A random group of 1,353 subjects aged between 40 and 70years was selected from a sample population of 596,478 individuals. Participants completed a questionnaire and then performed spirometry with bronchodilator testing if obstruction was observed. COPD was diagnosed when the post-bronchodilator FEV1/FVC ratio was less than 0.70. RESULTS: The prevalence of COPD was 7.3% (95%CI: 5.5-9.5) and was higher in males than in females (8.7% vs. 6.3%, P=.134). The incidence of smoking was 29.4% (95%CI: 25.4-33.1) and was also higher in males than in females (35.1% vs 25.4%, P<.001). The prevalence of COPD stratified by severity of obstruction, according to the GOLD criteria, was 16% in groupi, 69.9% in groupii, 10.4% in groupiii and 3.3% in groupiv. 71.6% of the subjects were underdiagnosed and 63.5% undertreated. CONCLUSIONS: Despite having one of the highest rates of smoking in Spain, the prevalence of COPD in the Canary Islands is lower than in most of the Spanish regions studied.

Long-term inhaled nitric oxide plus phosphodiesterase 5 inhibitors for severe pulmonary hypertension.

BACKGROUND: Inhaled nitric oxide (iNO) is a potent pulmonary vasodilator, but therapeutic experience in patients with severe pulmonary hypertension is scarce. METHODS: Eleven patients with severe pulmonary hypertension, 6 due to pulmonary arterial hypertension and 4 due to chronic thromboembolic disease, were selected for iNO therapy. A phosphodiesterase type 5 inhibitor (PDE5i) was added in cases of clinical worsening. In this study we evaluate the clinical effectiveness and safety of long-term treatment with iNO either alone or combined with a PDE5i. RESULTS: After 1 month of iNO administration, improvements were observed in World Health Organization functional class, Borg scale (p = 0.003), brain natriuretic peptide levels (p = 0.002) and 6-minute walk test (p = 0.003). After 6 months of treatment, 7 patients had clinical deterioration that was reversed upon adding a PDE5i. One of these patients died in Month 8 and another underwent pulmonary transplantation in Month 9. The clinical condition of the remaining 9 patients was unchanged after 1 year. A second right catheterization showed improvement in mean pulmonary arterial pressure (66 +/- 15 mm Hg to 56 +/- 18 mm Hg; p = 0.01), pulmonary vascular resistance (1,234 +/- 380 dyn/s/cm(5) to 911 +/- 410 dyn/s/cm(5); p = 0.008) and cardiac index (2.0 +/- 0.4 liters/min/m(2) to 2.5 +/- 0.4 liters/min/m(2); p = 0.04). There was no significant increase in methemoglobin, no worsening of pulmonary function and no sudden withdrawal syndrome. CONCLUSIONS: We suggest that iNO therapy alone or in combination with a PDE5i could be a therapeutic alternative for severe pulmonary hypertension.

Usefulness of cephalometry in sparing polysomnography of patients with suspected obstructive sleep apnea.

The aim of this investigation was to evaluate the contribution of cephalometry to a statistical model integrating clinical, physical, and oximetric variables, to reduce demands for polysomnographies. Two hundred and twenty-five consecutive patients that had been referred to the sleep clinic for suspected obstructive sleep apnea (OSA) were studied. The clinical assessment of all patients consisted of a sleep related questionnaire, the Epworth sleepiness scale, and a physical examination. In addition, they all underwent spirometry, cephalometry, and a full polysomnography. The clinical variables related with OSA were questions concerning witnessing of apneas by bed partners, intensity of snoring, a history of hypertension, and nocturia. A significant relation was also found with score on the Epworth scale, sex, age, body mass index, neck and waist circumferences, total number and frequency of oxygen desaturations, and the lowest oxygen saturation value. Significant cephalometric measurements were: the linear distance from gonion to gnathion, from the hyoid bone to the mandibular plane, and from the posterior nasal spine to the tip of the soft palate, and the thickness of the uvula as well. A statistical model was built to estimate a patient's probability of having OSA based on clinical variables, physical examination, pulse oximetry, and cephalometry. The validation of this model demonstrated a remarkable ability in reducing the number of polysomnographic studies. We conclude that cephalometry combined with clinical variables, physical examination, and nocturnal oximetry is useful in the diagnosis of OSA and enables the sparing of a considerable number of polysomnographies.

Long-term inhaled nitric oxide plus dipyridamole for pulmonary arterial hypertension.

Inhaled nitric oxide (iNO) has been shown to be a potent and selective vasodilator in pulmonary arterial hypertension (PAH). However, the clinical experience in prolonged treatment is limited. We assess the safety and effectiveness of long-term administration of iNO in severe PAH. Two female patients were admitted to our hospital because of severe dyspnea (World Health Organization functional class IV) and hypoxemia. They were diagnosed with PAH (primary and secondary to congenital heart disease) and treated with iNO for 2 years. The delivery system consisted of an NO tank of 800 ppm, a modified gas-pulsing device, and nasal cannulas. On iNO treatment the patients showed remarkable improvement of symptoms, oxygenation and 6-min walk distance. After 16 months the patients began to experience a progressive rebound of symptoms. A phosphodiesterase type 5 inhibitor (dipyridamole) was added to iNO. This intervention proved useful in improving clinical deterioration and hemodynamics. This is the first study reporting 2-year iNO therapy in 2 patients with primary and secondary pulmonary hypertension. The combination of dipyridamole with iNO augments the pulmonary vasodilatation and may be useful in managing PAH.