Can static hyperinflation predict exercise capacity in COPD?

INTRODUCTION: The diagnosis and severity assessment of COPD relies on spirometry, and in particular the FEV1. However, it has been proposed that hyperinflation and air-trapping are better predictors of exercise capacity and mortality than the FEV1. RESEARCH: QUESTION: Does static hyperinflation predict exercise capacity? METHODS: We conducted an observational prospective study. Patients with COPD referred to the lung function laboratory were consecutively recruited. Patients with hyperinflation (the experimental group) were compared to patients without hyperinflation (the control group). The sample sizes were determined assuming an effect size of 0.5 and a power of 0.80. RESULTS: We recruited 124 participants, of whom 87% were male, the mean age was 66.1 ± 8.8 years. 67% were symptomatic (GOLD B or D). Airflow limitation was moderate to severe in the majority of patients (median FEV1 47%, IQR 38-65%) and 43% of patients had static hyperinflation. The median 6MWD was 479 meters (404-510) and peak workload in CPET was 64 watts (46-88) with peak VO2 1.12 L/min, 0.89-1.31 L/min. Patients with lower FEV1, DLCO and IC/TLC and higher RV/TLC had reduced exercise capacity in both 6MWT and CPET, measured as lower distance, greater desaturation and ∆Borg dyspnoea, and reduced workload, peak VO2 and peak VE and higher desaturation and ventilatory limitation (VE/MVV). An IC/TLC < 0.33 predicted reduced exercise performance (peak O2 <60%). Dyspnoea assessed by mMRC and QoL measured by CAT and CCQ were also worse in the hyperinflation in COPD patients. CONCLUSION: In COPD patients, IC/TLC and RV/TLC are valuable predictors of exercise performance in both 6MWT and CPET and PRO.

Obtaining spirometric reference values when height is not available - comparison of alternative anthropometric measures.

INTRODUCTION: Height is one of the variables used to derive reference values for respiratory function but it is not always available. To fulfil this need, different formulas are described in literature. AIM: To understand which method best estimate height in order to obtain Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1st second (FEV1) reference values. METHODS: The true stature (TS) and five alternative anthropometric measures that estimate height [arm span using a regression equation (ASR), arm span using a fix correction factor (ASF), half arm span, knee height and ulnar length] were measured for all patients. To assess the differences between the TS versus the estimated heights and the respective reference values of FVC and FEV1, T Student Test and Wilcoxon test were used. Agreement was evaluated by Intraclass Correlation Coefficient and by Bland-Altman plot. RESULTS: A total of 160 subjects were recruited but 14 patients were excluded due to skeletal deformities. The predicted FVC and FEV1 using all alternative anthropometric measures were statistically different from those calculated by TS, except for ASF. The limits of agreement were wide for all alternative measures. With the exception of ASF, predicted FVC and FEV1 were overestimated when using all other alternative measures. CONCLUSIONS: For the purpose of replacing height in order to obtain predicted values of FVC and FEV1, the ASF was shown to be the most accurate and recommendable method. However, we must be aware there is a possible degree of error.

Severe asthma in obese patients: Improvement of lung function after treatment with omalizumab.

INTRODUCTION: Asthma and obesity have a considerable impact on public health and their prevalence is increasing. Obesity is a known risk factor for asthma and can make it more difficult to control. Omalizumab is recommended in patients with severe allergic persistent asthma. The aim of this study was to assess the impact of omalizumab treatment in obese asthmatic patients with poorly controlled severe persistent asthma. METHODOLOGY: A non-interventional, prospective study was conducted, in an outpatient asthma clinic. All patients with severe asthma who started treatment with omalizumab were included and followed over 12 months. The study population was divided into two groups (obese and non-obese) for statistical analysis (descriptive and comparative analysis). RESULTS: Thirty-two patients (19 obese) were followed. After 12 months of omalizumab treatment, there was a statistically significant improvement in body mass index, number of exacerbations in the previous year, rescue medication, disease control and lung function, in the whole population. At the end of the study obese patients had a significantly better lung function (FEV1) than non-obese. DISCUSSION: As described in the literature, there was a significant reduction in the number of exacerbations in the previous year, rescue medication and better disease control, in the whole population. In relation to lung function, about which published data are inconsistent, treatment with omalizumab significantly improved it in obese patients. CONCLUSION: Our study showed that omalizumab significantly improved asthma control, reduced rescue medication and asthma exacerbations in all the population; and for the first time showed that obese patients achieved significantly improved lung function.

Reference equations for the 6-minute walk distance in healthy Portuguese subjects 18-70 years old.

INTRODUCTION: Six-minute walk test (6MWT) is used for evaluating functional exercise capacity. To the best of our knowledge, there are no reference equations to predict six-minute walk distance (6MWD) for the Portuguese population. The aims of the present study were to measure anthropometric data and 6MWD in a sample of healthy Portuguese population, to establish reference equations to predict 6MWD and to compare our equations with those obtained by previously published studies. METHODS: We conducted an observational prospective study. We consecutively recruited 158 healthy 18-70 years old subjects from Porto district, who performed two 6MWTs using a standardized protocol. The best 6MWD was used for further analysis. RESULTS: The mean 6MWD was 627.8m (SD=73.3m). The variables that were significantly associated with the 6MWD were age, sex, BMI and ΔHR (Heart Rateat the end of the test-HRat rest). We found three explanatory models for 6MWD, the best with an explanatory power of 38%: 6MWD=721.7-1.6×Age-4.0×BMI+0.9×ΔHR+58.4×Sex. We verified that 6MWD decreased 1.6m per year of age, and 4.0m per unit of BMI and increased 0.892m per beat per minute. Moreover, on average, males walk 58.4m more than females (p<0.001). Applying equations from other studies to our population resulted in an overestimation or underestimation of the 6MWD. CONCLUSION: The present study was the first to describe the 6MWD in healthy Portuguese people aged 18-70 years old and to propose predictive equations. These can contribute to improving the evaluation of Caucasian Mediterranean patients with diseases that affect their functional capacity.

Role of the impulse oscillometry in the evaluation of tracheal stenosis.

INTRODUCTION AND OBJECTIVES: Tracheal stenosis is a rare and challenging disease. Bronchoscopy is the gold standard for diagnosis and assessment but brings inherent risks. Spirometry is commonly used to access obstructions but is not always feasible due to patient related factors. We therefore considered impulse oscillometry (IOS) as a non-invasive method to quantify airway obstruction and its potential use for diagnosis and follow-up of tracheal stenosis. MATERIALS AND METHODS: Patients with confirmed tracheal stenosis were recruited between January 1st, 2015 and December 31st, 2016. Before bronchoscopy, all subjects underwent IOS and spirometry; for patients submitted to interventional bronchoscopy the same techniques were also performed after the procedure. We assessed the correlation between IOS measurements and airway narrowing as well as between IOS and spirometry values. RESULTS: Twenty-one patients were included. Tracheal narrowing was inversely correlated with X5% (r -0.442, p 0.045) and positively correlated with FEV1/PEF (r 0.467, p 0.033). The stenosis length was inversely correlated with PEF and PEF% (r -0.729, p=0.001 and r -0.707, p=0.002, respectively). There was a strong correlation between spirometric and IOS values. We did not find any significant differences between pre- and post-intervention IOS values for patients assessed after interventional bronchoscopy. CONCLUSIONS: Our study showed a weak correlation between X5% and tracheal narrowing making it unclear whether IOS can be used for physiological assessment of patients with tracheal stenosis. Stenosis length correlated with PEF making it a potential predictor of successful surgical approach. The correlation between IOS and spirometric values makes IOS a potential alternative in patients with suspected tracheal stenosis who are not able to perform spirometry. Larger scale studies should clarify the role of IOS in this pathology.

Does any association exist between Chronic Obstructive Pulmonary Disease and Erectile Dysfunction? The DECODED study.

INTRODUCTION: Erectile dysfunction (ED) is the inability to achieve or maintain an erection for satisfactory sexual activity. Recent studies have shown an association between ED and chronic obstructive pulmonary disease (COPD). However, this issue is often ignored. We aimed to evaluate the ED prevalence in COPD patients and its risk factors and to study the impact of dyspnea in sexual activity. METHODS: Cross-sectional study that included sexually active male patients with COPD. The International Index of Erectile Function (IIEF-5) questionnaire evaluated ED and the Respiratory Experiences with Sexuality Profile (RESP) was used to evaluate the impact of dyspnea on sexual activity. Risk factors for mild-moderate or moderate ED were determined using logistic regression. RESULTS: 84 patients were consecutively assessed for eligibility, 67 were included (median age: 65 years, 13% never-smokers). Twenty two percent had COPD 2011-GOLD A; 22% GOLD B, 14% GOLD C and 42% GOLD D. Fifty-eight patients (87%) had some degree of ED: 26 (45%) mild, 20 (34%) mild-moderate and 12 (21%) moderate ED. ED occurred in all GOLD stages of COPD, mainly in GOLD B and D stages. Higher CAT score was independently associated to mild-moderate/moderate ED. Most patients (85%) reported dyspnea during their sexual activity but 72% had never talked about it with their physician. CONCLUSIONS: ED is highly prevalent among COPD patients and it is more severe in patients with higher CAT scores. Dyspnea affects their sexual activity but this is not a topic often discussed between patients and doctors, something which needs to be improved.

Ocular tuberculosis: Position paper on diagnosis and treatment management.

Delay in diagnosis or treatment of ocular tuberculosis can result in loss of vision. However, due to the fact that early diagnosis is rarely achieved, there are still a broad variety of diagnostic and treatment approaches. Our aim was to reach a consensus on the management of diagnosis and treatment of ocular tuberculosis. METHODS: Critical appraisal of the literature and expert opinion on diagnosis and treatment of ocular tuberculosis. RESULTS AND CONCLUSION: The currently recommended method for ocular TB diagnosis is screening for tuberculosis in any uveitis of unknown etiology, recurrent or not responding to conventional therapy; in ocular findings highly suggestive of ocular TB and before immunosuppression (particularly biologic agents). TB screening in these cases includes tuberculosis skin testing and interferon gamma testing, along with complete medical history, ophthalmologic evaluation and chest imaging. Positively screened patients should be treated for active tuberculosis with 4 drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) for 6-9 months. Patients should be reviewed at the end of the initiation phase (two months) and at the end of the overall treatment (6-9 months).

Diffuse vascular hamartoma with malignant behavior.

Pulmonary hamartomas are benign lesions, usually asymptomatic and incidentally discovered on a routine chest radiograph; occasionally, however, this benign lesion may cause life threatening symptoms due to it's location and diffuse vascular involvement. We report the case of a 27 year-old male, non-smoker, who presented with dyspnea, cough, hemoptysis and weight loss. He was found to have a mass in the right hilar region which also involved the right main bronchus, pulmonary artery and esophagus. Surgical biopsy of the lesion led to the diagnosis of diffuse vascular hamartoma. Although it was a benign lesion, due to the size and location, surgical removal was not possible and patient died 10 years after being diagnosed with the condition.

Alpha-1 antitrypsin deficiency caused by a novel mutation (p.Leu263Pro): Pi*ZQ0gaia - Q0gaia allele.

Severe alpha-1 antitrypsin deficiency (AATD) is generally associated with PI*ZZ genotype and less often with combinations of PI*Z, PI*S, and other rarer deficiency or null (Q0) alleles. Severe AATD predisposes patients to various diseases, including pulmonary emphysema. Presented here is a case report of a young man with COPD and AATD. The investigation of the AATD showed a novel mutation p.Leu263Pro (c.860T>C), which was named Q0gaia (Pi*ZQ0gaia). Q0gaia is associated with very low or no detectable serum concentrations of AAT.

The overall impact of COPD (CAT) and BODE index on COPD male patients: correlation?

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) will be the 5th leading cause of disability (DALYs) and the 4th leading cause of death by 2030. Measuring the real impact of COPD using CAT ("COPD Assessment Test") can complement BODE index, an indicator of mortality. AIMS: To assess correlation between CAT and BODE index in COPD patients. MATERIALS AND METHODS: A retrospective study was conducted in a population of patients with COPD in a Respiratory Rehabilitation program. We analyzed demographic variables, variables in respiratory function--6 min walking test (6 MWT), post-BD forced expiratory volume in 1st second (FEV1%); dyspnea by mMRC scale; BODE Index and CAT. RESULTS: The study included 50 patients--GOLD stage I (7), II (25), III (14) and IV (4), 48 men; mean age 62.6 years (± 9.5), average BMI 25.8 kg/m(2) (± 4.8) and FEV1 57.1% (± 19.6); 6 MWT of 443.3m (± 61.6); 46% patients in classes 2 and 3 of mMRC scale; 84% were class 2 in BODE Index. About 80% reported slight to medium impact in CAT. CAT score and impact were correlated with BODE index score: R=0.475, p<0.01, and R=0.377, p=0.004, and BODE index class: R=0.357, p=0.011, and R=0.326, p=0.021. CONCLUSION: As pre-existent data in the literature (exacerbations and benefit of rehabilitation in COPD), the positive correlations found with BODE index reinforce the discriminative validity of CAT as a complement in the evaluation of what the true impact of COPD is on a patient's daily life.

Confirming the diagnosis of tuberculosis in children in Northern Portugal.

Childhood tuberculosis (TB) is difficult to diagnose and there are no standardised case definitions. TB records of patients aged >5 years reported in Northern Portugal between 2000 and 2009 were reviewed. Of the 116 children diagnosed with TB, 72 (62.1%) were male; the mean age was 2.2 ± 1.2 years. Of the 32 children (27.6%) with confirmed TB, only 46.7% had provided samples for culture, showing that little effort is made to obtain specimens for confirmation. We could not identify independent factors associated with the low rate of sample collection or anti-tuberculosis treatment without confirmation; chest radiography lesions were less frequent in children who began treatment without confirmation (adjusted OR 0.23, 95%CI 0.05-0.98).

WITHDRAWN: The overall impact of COPD (CAT) and BODE index on COPD male patients: correlation?

This article has been withdrawn for editorial reasons because the journal will be published only in English. In order to avoid duplicated records, this article can be found at http://dx.doi.org/10.1016/j.rppnen.2014.02.004. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Pneumococcal pneumonia - Are the new severity scores more accurate in predicting adverse outcomes?

INTRODUCTION: The site-of-care decision is one of the most important factors in the management of patients with community-acquired pneumonia. The severity scores are validated prognostic tools for community-acquired pneumonia mortality and treatment site decision. The aim of this paper was to compare the discriminatory power of four scores - the classic PSI and CURB65 ant the most recent SCAP and SMART-COP - in predicting major adverse events: death, ICU admission, need for invasive mechanical ventilation or vasopressor support in patients admitted with pneumococcal pneumonia. METHODS: A five year retrospective study of patients admitted for pneumococcal pneumonia. Patients were stratified based on admission data and assigned to low-, intermediate-, and high-risk classes for each score. Results were obtained comparing low versus non-low risk classes. RESULTS: We studied 142 episodes of hospitalization with 2 deaths and 10 patients needing mechanical ventilation and vasopressor support. The majority of patients were classified as low risk by all scores - we found high negative predictive values for all adverse events studied, the most negative value corresponding to the SCAP score. The more recent scores showed better accuracy for predicting ICU admission and need for ventilation or vasopressor support (mostly for the SCAP score with higher AUC values for all adverse events). CONCLUSIONS: The rate of all adverse outcomes increased directly with increasing risk class in all scores. The new gravity scores appear to have a higher discriminatory power in all adverse events in our study, particularly, the SCAP score.

Two types of omega-agatoxin IVA-sensitive Ca2+ channels are coupled to adrenaline and noradrenaline release in bovine adrenal chromaffin cells.

To clarify the role of P-type Ca2+ channels in catecholamine release from adrenal chromaffin cells we examined the concentration dependence of the effect of omega-agatoxin IVA on the release both of adrenaline and noradrenaline induced by a K(+)-evoked depolarization. omega-Agatoxin IVA caused a biphasic dose-dependent inhibition of secretion with a high-potency component (IC50 < 1 nM), responsible for 10-15% of catecholamine release evoked by 70 mM K+, and a low-potency component that accounted for about 40% of release, with IC50 values of 57 nM and 48 nM for noradrenaline and adrenaline release, respectively. The release of catecholamines from chromaffin cells was also inhibited dose dependently by omega-conotoxin MVIIC with IC50 values of 182 and 218 nM for noradrenaline and adrenaline release, respectively. The effects of 3 nM omega-agatoxin IVA and 3 microM omega-conotoxin MVIIC were additive, indicating that at the concentrations used the toxins were acting at independent sites, presumably, P- and Q-type Ca2+ channels. The blockade of Q-type channels inhibited the release of adrenaline (72 +/- 4.1%) significantly more than the release of noradrenaline (50 +/- 2.7%), suggesting a higher density or a closer coupling of these channels to exocytosis in adrenergic chromaffin cells. The blockade of P-type channels caused a greater inhibition of catecholamine secretion at low levels of K(+)-evoked depolarization and shorter times of stimulation than that observed at higher levels of stimulation. The contribution of Q-type channels to catecholamine secretion did not change significantly with the intensity of stimulation. The data show that two types of omega-agatoxin IVA-sensitive Ca2+ channels are coupled to catecholamine release in chromaffin cells, and that the contribution of P-type channels to secretion is larger at low levels of depolarization.