Prediction of COPD by the single-breath nitrogen test and various respiratory symptoms.

Early identification of subjects running an increased risk of contracting COPD enables focus on individual preventive measures. The slope of the alveolar plateau of the single-breath nitrogen washout test (N2-slope) is a sensitive measure of small-airway dysfunction. However, its role remains unexplored in predicting hospital admission or death related to COPD, i.e. incident COPD events, in relation to the presence of various respiratory symptoms. A random population sample of 625 men, aged 50 (n=218) or 60 years (n=407), was followed for 38 years for incident COPD events. At baseline, a questionnaire on respiratory symptoms and smoking habits was collected, spirometry and the single-breath nitrogen test were performed, and the N2-slope was determined. Proportional hazard regression (Cox regression) analysis was used for the prediction model. The N2-slope improved the prediction of COPD events significantly beyond that of respiratory symptoms weighted all together and other covariates (hazard ratio 1.63, 95% CI 1.20-2.22; p<0.005), a prediction applicable to subjects without (p=0.001) and with (p<0.05) airway obstruction. Dyspnoea and wheezing were the most predictive symptoms. The combination of the N2-slope and number of respiratory symptoms notably resulted in an effective prediction of incident COPD events even in nonobstructive subjects, as evidenced by a predicted incidence of ∼70% and ∼90% for a very steep N2-slope combined with many respiratory symptoms in subject without and with airway obstruction, respectively. The alveolar N2-slope should be considered in the critical need for further research on early diagnosis of COPD.

Prediction of COPD and Related Events Improves by Combining Spirometry and the Single Breath Nitrogen Test.

Chronic obstructive pulmonary disease (COPD) develops in small airways. Severity of small airway pathology relates to progression and mortality. The present study evaluated the prediction of COPD of a validated test for small airway disease, i.e. a slope of the alveolar plateau of the single breath nitrogen test (N2-slope). The N2-slope, spirometry, age, smoking habits, and anthropometric variables at baseline were obtained in a population-based sample (n = 592). The cohort was followed for first COPD events (first hospital admission of COPD or related conditions or death from COPD) during 38 years. During follow-up, 52 subjects (8.8%) had a first COPD event, of which 18 (3.0%) died with a first COPD diagnosis. In the proportional hazard regression analysis adjusted for age and smoking habits, the cumulative COPD event incidence increased from 5% among those with high forced expired volume in one second (FEV1) to 25% among those with low FEV1, while increasing from 4% among those with the lowest N2-slope to 26% among those with the highest. However, combining the N2-slope and FEV1 resulted in considerable synergy in the prediction of first COPD event and even more so when taking account of smoking habits. The cumulative COPD event incidence rate was 75% among heavy smokers with the highest N2-slope and lowest FEV1, and less than 1% among never smokers with the lowest N2-slope and highest FEV1. Thus, combining the results of the single breath N2-slope and FEV1 considerably improved the prediction of COPD events as compared to either test alone.

The single breath nitrogen test and mortality--A 38 years follow up.

BACKGROUND: Spirometry data predict mortality, but are less sensitive to detect dysfunction in small airways as compared to the slope of phase III (the N2 slope) of the single breath nitrogen test. The association between the N2 slope and mortality has been studied with conflicting results. In the present study the prognostic importance of the N2 slope was tested taking spirometry variables into account. METHODS: A systematic general population sample of 595 middle-aged men had a baseline investigation with lung function tests including spirometry and the N2 slope. Age, smoking, and anthropometry variables were registered. The cohort was followed up regarding survival for 38 years. RESULTS: The sample was subdivided by tertiles of the N2 slope. A proportional hazards regression analysis was performed for each group of covariates: anthropometric, smoking variables, and spirometry variables, after accounting for age. Covariates with significant impact on mortality and the highest chi-square levels were smoking habit score and forced expired volume in 1 s corrected for height. These variables, in addition to age and the N2 tertiles were entered into a final proportional hazards regression analysis. In this multivariate model, mortality was significantly related to age (p < .0001), smoking habit score (p < .0001) and the N2 tertiles (p = .0004), but not to FEV1 when N2 slope was allowed for in the model. CONCLUSIONS: Dysfunction in small airways as measured by the N2 slope is significantly associated with overall mortality in middle-aged men, and outrivals spirometry as a predictor in multivariate analysis.

The impact of individual quality of life assessment on psychosocial attention in patients with chest malignancies: a randomized study.

PURPOSE: The aims of this study were to investigate the impact of individual health-related quality of life (HRQL) evaluation on the attention towards symptom control and psychosocial function in advanced cancer patients. METHODS: Patients with advanced lung cancer or mesothelioma who attended a pulmonary oncology outpatient clinic were randomized to either of two strategies for HRQL assessment. The experimental group (EG) answered the EORTC QLQ-C30 + LC13 questionnaire using a digital table interface, with outprint of aggregated scale scores presented to the consulting physician as a support for evaluation. The control group (CG) answered a paper version of the same questionnaire, which was stored for later analysis. Consultations were audio-recorded. Outcome measures were a quantitative content analysis of audio-recorded consultations and medical and psychosocial interventions abstracted from clinical records. RESULTS: One hundred seventy-one patients were randomized and participated in the study. Issues regarding emotional function were more frequently discussed during consultations in the EG (p < 0.05). Similarly, interventions directed to emotional and social concerns were more frequent in the EG (p = 0.013 and p = 0.0036, respectively). HRQL measures over time were similar across the groups. CONCLUSION: Individual HRQL assessment increased the attention to psychosocial functioning in patients with chest malignancies.

Respiratory symptoms and peripheral airways disease in a cross-sectional study on a random population sample.

OBJECTIVES: Respiratory symptoms are associated with spirometry results but more strongly with smoking history, suggesting that alterations in the lung other than those revealed by spirometry contribute to cause symptoms. Smoking may cause obstruction of peripheral airways that is poorly detected by spirometry. The slope of phase III of the single-breath nitrogen (N(2)) test detects smoking-induced alterations in smokers before spirometry is impaired. The aim of the present investigation was to study the association between respiratory symptoms and the slope of phase III adjusting for spirometry results and smoking history. DESIGN: Single-centre retrospective cross-sectional study. SETTING: University hospital in Gothenburg, Sweden. PARTICIPANTS: A random population sample of 430 elderly men. METHODS: The presence of seven different respiratory symptoms were analysed by a multiple logistic regression model in relation to spirometry results, smoking history (pack-years) and the slope of phase III in a population sample of 430 elderly men, age span 50-67 years. Furthermore, smoking normalised values of the slope of phase III were calculated and differences between subjects reporting/not reporting symptoms were tested. RESULTS: The presence of some cough symptoms was significantly associated with a steep slope of phase III also when adjusting for spirometry results and smoking history. Furthermore, smoking normalised slope of phase III was significantly steeper among subjects with cough symptoms compared to those without cough symptoms. CONCLUSIONS: Cough symptoms may be an effect of abnormalities in peripheral airways at least among elderly men.

Qualify of life and palliation predict survival in patients with chronic alveolar hypoventilation and nocturnal ventilatory support.

OBJECTIVES: Non-invasive positive pressure ventilation (NPPV) improves health-related quality of life (HRQL) in patients with chronic alveolar hypoventilation (CAH). We studied the prognostic impact of HRQL on survival in relation to clinical factors. PATIENTS: Forty-four patients with CAH due to post-polio (12), scoliosis (11), post-tb (17) or other diagnoses (4) who received nocturnal NPPV were prospectively studied during 6-10 years. MEASUREMENTS: Blood gases and HRQL were analysed at baseline and after 9 months and after 8 years. HRQL was evaluated with measures of functioning (SIP), emotional well-being (HADS and MACL), and global QL. RESULTS: Blood gases and HRQL measures improved during NPPV. The overall 5-year survival rate was 73%. In multivariate survival analysis, a diagnosis of post-polio and low baseline SIP physical index scores, indicating low levels of physical dysfunction, predicted longer survival (P = 0.02, respectively). Similarly, palliation of physical dysfunction and preserved or improved global QL by 9 months were associated with longer overall survival (P = 0.009 and P = 0.001, respectively; multivariate Cox regression). CONCLUSION: Seventy-three percent of patients treated for CAH with NPPV survived more than 5 years. Diagnosis and self-rated physical functioning at pre-treatment were related to survival, as were major improvements in physical functioning and global QL during NPPV.

Impact of home mechanical ventilation on health-related quality of life in patients with chronic alveolar hypoventilation: a prospective study.

BACKGROUND: Nocturnal ventilatory support by nasal positive pressure ventilation (NPPV) is an established treatment method in patients with chronic alveolar hypoventilation (CAH). The knowledge about its long-term effects on health-related quality of life (HRQL) is limited. METHODS: In a prospective, longitudinal, single-strand study, patients with CAH caused by non-COPD conditions, consecutively recruited among referral patients in three Swedish university hospital pulmonary departments, were examined at baseline and after 9 months (n = 35) and 8 years (n = 11) on NPPV treatment. Both volume pre-set and pressure pre-set ventilators were used. Patients completed a battery of condition-specific and generic HRQL questionnaires at baseline and follow-up. Spirometry and blood gases were measured. Compliance with treatment, side effects and patient satisfaction were evaluated. RESULTS: After 9 months of NPPV, improvements were seen primarily not only in sleep-related domains, but also in emotional behaviour, ambulation and sleep/rest functioning as measured with the Sickness Impact Profile (SIP). Improvements in sleep-related symptoms were related to effectiveness in ventilation, evaluated by morning PaCO(2), and remained by 8 years. Mental well-being was stable over time, while emotional distress improved by 8 years. Satisfaction with treatment was high in spite of frequent side effects. CONCLUSION: NPPV improves HRQL, particularly in condition-specific areas. Improvements are related to effectiveness in ventilation. Side effects are common, but compliance is good and patient satisfaction is high.

COPD 'diagnosis' based on spirometric reference equations.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is suspected if the ratio between forced expired volume in 1 s (FEV(1)) and forced vital capacity is below 0.7 after bronchodilatation, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). As this ratio varies with age and gender, the lower limit of normality (LLN) of appropriate reference equations appears more adequate. OBJECTIVES: To study the prevalences of suspected COPD according to the GOLD criterion and various reference equations in a well-defined population sample. METHODS: Spirometries obtained in a random population sample of 598 men, 50 or 60 years of age, were analysed. The prevalences of suspected COPD were calculated according to the GOLD criterion and the LLNs of four Nordic and two European reference equations. RESULTS: The GOLD criterion resulted in prevalences of COPD of 9.3% and 23.7% in the 50- and 60-year-old never-smokers, respectively. Depending on the reference equation, the calculated prevalences of COPD varied between 9.3% and 23.4% and 12.0% and 39.1% among all of the 50- and 60-year-old men, respectively. CONCLUSIONS: The GOLD criterion is inadequate because of substantial overestimation in 60-year-old never-smokers. LLNs of the various reference equations are unreliable because of obvious lack of consistency. Spirometric criteria for airway obstruction, and suspicion of COPD, therefore need to be revised.

Tumour-associated macrophages secrete IL-6 and MCP-1 in head and neck squamous cell carcinoma tissue.

Conclusion. Tumour-associated macrophages (TAMs) in head and neck squamous cell carcinomas (HNSCCs) secrete interleukin 6 (IL-6) and monocyte chemotactic protein (MCP-1) that can be down-regulated by L-leucine-methylester (LLME); however, there is no qualitative difference between function of TAMs and tissue macrophages in mucosa as measured by IL-6 and MCP-1 secretion. Objectives. TAMs play an important role in the interaction with tumour cells in malignant tumours. The cells in the tumours that are the main sources of the various signal substances need to be further elucidated. The aim of this investigation was to reveal whether TAMs in HNSCCs secrete IL-6 and MCP-1. These cytokines influence tumour cell growth and macrophage influx in tumours, respectively. Materials and methods. In order to inhibit macrophage function in F-spheroids, in some experiments the tissue fragments were initially incubated with LLME, a substance that selectively inhibits function of phagocytes. IL-6 and MCP-1 secretion from untreated F-spheroids was compared to cytokine secretion from LLME-treated F-spheroids as measured by ELISA. Results. LLME did not affect the viability of F-spheroids and reduced IL-6 and MCP-1 secretion from monocyte-derived macrophages in vitro. F-spheroids from LLME-treated tissue fragments showed lower IL-6 and MCP-1 secretion compared with F-spheroids from tissue fragment untreated with LLME.

Diaphragmatic function in advanced Duchenne muscular dystrophy.

The aim of this study was to assess diaphragm electrical activation and diaphragm strength in patients with advanced Duchenne muscular dystrophy during resting conditions. Eight patients with advanced Duchenne muscular dystrophy (age of 25 +/- 2 years) were studied during tidal breathing, maximal inspiratory capacity, maximal sniff inhalations, and magnetic stimulation of the phrenic nerves. Six patients were prescribed home mechanical ventilation (five non-invasive and one tracheotomy). Transdiaphragmatic pressure and diaphragm electrical activation were measured using an esophageal catheter. During tidal breathing (tidal volume 198 +/- 83 ml, breathing frequency 25 +/- 7), inspiratory diaphragm electrical activation was clearly detectable in seven out of eight patients and was 12 +/- 7 times above the noise level, and represented 45 +/- 19% of the maximum diaphragm electrical activation. Mean inspiratory transdiaphragmatic pressure during tidal breathing was 1.5 +/- 1.2 cmH2O, and during maximal sniff was 7.6 +/- 3.6 cmH2O. Twitch transdiaphragmatic pressure deflections could not be detected. This study shows that despite near complete loss of diaphragm strength in advanced Duchenne muscular dystrophy, diaphragm electrical activation measured with an esophageal electrode array remains clearly detectable in all but one patient.