Supranormal lung function: Prevalence, associated factors and clinical manifestations across the lifespan.

BACKGROUND AND OBJECTIVE: It is now well established that there are different life-long lung function trajectories in the general population, and that some are associated with better or worse health outcomes. Yet, the prevalence, clinical characteristics and risk factors of individuals with supranormal FEV1 or FVC values (above the upper-limit of normal [ULN]) in different age-bins through the lifetime in the general population are poorly understood. METHOD: To address these questions, we investigated the prevalence of supranormal FEV1 and FVC values in the LEAD (Lung, hEart, sociAl and boDy) study, a general population cohort in Austria that includes participants from 6 to 82 years of age. RESULTS: We found that: (1) the prevalence of supranormal pre-bronchodilator FEV1 and FVC values was 3.4% and 3.1%, respectively, and that these figures remained relatively stable through different age-bins except for participants >60 years., in whom they increased (5.0% and 4.2%, respectively). Approximately 50% of supranormal individuals had both increased FEV1 and FVC values; (2) supranormal spirometric values were consistently accompanied by higher static lung volumes and lower specific airway resistance through the lifespan, indicating better overall lung function; and (3) multivariate regression analysis identified that female sex, higher muscle mass (FFMI), less diabetes and fewer respiratory symptoms were consistently associated with supranormal FEV1 and FVC values. CONCLUSION: Supranormal FEV1 and/or FVC values occur in about 3% of the general population in different age bins and are associated with better health markers.

Prevalence of restrictive lung function in children and adults in the general population.

BACKGROUND: Restrictive lung function (RLF) is characterized by a reduced lung expansion and size. In the absence of lung volume measurements, restriction can be indirectly assessed with restrictive spirometric patterns (RSP) by spirometry. Prevalence data on RLF by the golden standard body plethysmography in the general population are scarce. Therefore, we aimed to evaluate the prevalence of RLF and RSP in the general population by body plethysmography and to determine factors influencing RLF and RSP. METHODS: Pre-bronchodilation lung function data of 8891 subjects (48.0% male, age 6-82 years) have been collected in the LEAD Study, a single-centered, longitudinal, population-based study from Vienna, Austria. The cohort was categorized in the following groups based on the Global Lung Initiative reference equations: normal subjects, RLF (TLC < lower limit of normal (LLN)), RSP (FEV1/FVC ≥ LLN and a FVC < LLN), RSP only (RSP with TLC ≥ LLN). Normal subjects were considered those with FEV1, FVC, FEV1/FVC and TLC between LLN and ULN (upper limit of normal). RESULTS: The prevalence of RLF and RSP in the Austrian general population is 1.1% and 4.4%. Spirometry has a positive and negative predictive value of 18.0% and 99.6% to predict a restrictive lung function. Central obesity was associated with RLF. RSP was related to smoking and underweight. CONCLUSIONS: The prevalence of true restrictive lung function and RSP in the Austrian general population is lower than previously estimated. Our data confirm the need for direct lung volume measurement to diagnose true restrictive lung function.

The LEAD (Lung, Heart, Social, Body) Study: Objectives, Methodology, and External Validity of the Population-Based Cohort Study.

BACKGROUND: The Lung, hEart, sociAl, boDy (LEAD) Study (ClinicalTrials.gov; NCT01727518; http://clinicaltrials.gov) is a longitudinal, observational, population-based Austrian cohort that aims to investigate the relationship between genetic, environmental, social, developmental and ageing factors influencing respiratory health and comorbidities through life. The general working hypothesis of LEAD is the interaction of these genetic, environmental and socioeconomic factors influences lung development and ageing, the risk of occurrence of several non-communicable diseases (respiratory, cardiovascular, metabolic and neurologic), as well as their phenotypic (ie, clinical) presentation. METHODS: LEAD invited from 2011-2016 a random sample (stratified by age, gender, residential area) of Vienna inhabitants (urban cohort) and all the inhabitants of six villages from Lower Austria (rural cohort). Participants will be followed-up every four years. A number of investigations and measurements were obtained in each of the four domains of the study (Lung, hEart, sociAl, boDy) including data to screen for lung, cardiovascular and metabolic diseases, osteoporosis, and cognitive function. Blood and urine samples are stored in a biobank for future investigations. RESULTS: A total of 11.423 males (47.6%) and females (52.4%), aged 6-80 years have been included in the cohort. Compared to governmental statistics, the external validity of LEAD with respect to age, gender, citizenship, and smoking status was high. CONCLUSIONS: In conclusion, the LEAD cohort has been established following high quality standards; it is representative of the Austrian population and offers a platform to understand lung development and ageing as a key mechanism of human health both in early and late adulthood.

Increased brachial intima-media thickness is associated with circulating levels of asymmetric dimethylarginine in patients with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an increased cardiovascular risk. However, the mechanisms for this association are yet unclear. The aim of this study was to investigate the relationship between brachial intima-media thickness (B-IMT), an independent predictor of cardiovascular risk, systemic inflammation, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in patients with COPD and respective controls. METHODS: The study sample consisted of 60 patients with stable COPD, free from overt cardiovascular disorders, as well as 20 smoking and 20 nonsmoking controls. Ultrasound assessment of B-IMT, spirometry, venous blood sampling for quantification of inflammatory markers and ADMA levels were carried out, and individual cardiovascular risk was calculated via the Framingham risk score. RESULTS: Patients with COPD showed significantly higher B-IMT compared to smoking (P=0.007) and nonsmoking controls (P=0.033). COPD patients with elevated B-IMT had a twofold increased calculated 10-year risk for cardiovascular events compared to those below the recommended cutoff (P=0.002). B-IMT was significantly associated with systemic inflammation (interleukin-6 [IL-6]; r=0.365, P=0.006) and ADMA (r=0.331, P=0.013) in COPD. Multivariate linear regression revealed male sex and ADMA as independent predictors of B-IMT in this study sample. CONCLUSION: B-IMT is significantly increased in patients with COPD and is associated with systemic inflammation and ADMA levels.

An update on the efficacy of endobronchial valve therapy in the management of hyperinflation in patients with chronic obstructive pulmonary disease.

Lung volume reduction surgery has been shown to be effective in patients with heterogeneous emphysema, but is also associated with a relatively high perioperative morbidity and mortality. Accordingly, several novel and potentially less invasive methods for bronchoscopic lung volume reduction have been developed. Endobronchial valve (EBV) therapy is one such therapeutic approach in patients with advanced emphysema. It has been the most widely studied technique over the past years and represents an effective treatment option for patients with severe heterogeneous upper- or lower-lobe-predominant emphysema. The choice of EBV therapy largely depends on the distribution of emphysema and the presence or absence of interlobar collateral ventilation. Adequate patient selection and technical success of valve implantation with the intention of lobar exclusion are predictive factors for positive outcomes. This review attempts to highlight the milestones in the development of bronchoscopic lung volume reduction with one-way valve implantation over the past few years.

Tobacco addiction and smoking cessation in Austrian migrants: a cross-sectional study.

OBJECTIVE: Recent observations revealed substantial differences in smoking behaviour according to individuals' migration background. However, smoking cessation strategies are rarely tailored on the basis of a migration background. We aimed to determine whether smoking behaviour and preferences for smoking cessation programmes differ between Austrian migrant smokers and Austrian smokers without a migration background. STUDY DESIGN: Cross-sectional study. SETTING: Recruitment and interview were performed at public places in Vienna, Austria. PARTICIPANTS: The 420 smokers included: 140 Bosnian, 140 Turkish migrant smokers of the first or second generation, as well as 140 Austrian smokers without a migration background. METHODS: We cross-sectionally assessed determinants of smoking behaviour and smoking cessation of every participant with a standardised questionnaire. PRIMARY OUTCOME MEASURE: The Fagerström Test for Nicotine Dependence. SECONDARY OUTCOME MEASURES: Determinants of smoking behaviour, willingness to quit smoking and smoking cessation. RESULTS: Nicotine addiction expressed via the Fagerström score was significantly higher in smokers with a migration background versus those without (Bosnian migrant smokers 4.7 ± 2.5, Turkish migrant smokers 4.0 ± 2.0, Austrian smokers without a migration background 3.4 ± 2.3, p<0.0001). Bosnian and Turkish migrant smokers described a greater willingness to quit, but have had more previous cessation trials than Austrian smokers without a migration background, indicating an increased demand for cessation strategies in these study groups. They also participated in counselling programmes less often than Austrian smokers without a migration background. Finally, we found significant differences in preferences regarding smoking cessation programmes (ie, preferred location, service offered in another language besides German, and group rather than single counselling). CONCLUSIONS: We found significant differences in addictive behaviour and cessation patterns between smokers with and without a migration background. Our results indicate a strong demand for adjusting cessation programmes to the cultural background.

Insulin resistance may contribute to vascular dysfunction in patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at an increased cardiovascular risk; however, the underlying mechanisms for this relationship are ill defined. Altered glucose metabolism may increase cardiovascular risk via impaired endothelial function. METHODS: We conducted a longitudinal pilot study to assess the interrelationship between systemic vascular function, glucose metabolism, and lung function in patients with COPD. Eighteen non-smoking patients with stable moderate-to-severe COPD [67 % male; median (first to third quartiles) Forced Expiratory Volume in 1 second (FEV1) % predicted: 38 % (28-55 %); body mass index: 26 kg/m(2) (24-28 kg/m(2))] free from cardiovascular risk factors were evaluated. Systemic vascular function was assessed by means of flow-mediated dilation technique of the brachial artery. Laboratory measurements included fasting blood glucose levels, circulating concentrations of insulin, C-reactive protein, and fibrinogen. Homeostatic model assessment of insulin resistance (HOMA-IR) was determined. Measurements were performed at baseline and were repeated after 12 months. RESULTS: Flow-mediated dilation significantly decreased from 13.5 % (11-15 %) at baseline to 9.8 % (6-12 %; p = 0.002) at the follow-up visit, whereas both fasting blood glucose concentrations and HOMA-IR increased from 94 mg/dl (86-103 mg/dl) to 102 mg/dl (94-111 mg/dl; p = 0.027) and from 1.2 (0.8-2.1) to 1.7 (1.2-3.0; p = 0.023), respectively. There was a significant relationship between changes in endothelial function and changes in fasting serum glucose (r = - 0.483, p = 0.009), HOMA-IR (r = - 0.441, p = 0.019), and FEV1 (r = 0.336, p = 0.05). CONCLUSION: Altered glucose metabolism may be associated with progression of endothelial dysfunction in patients with COPD.

Sleep profile and symptoms of sleep disorders in patients with stable mild to moderate chronic obstructive pulmonary disease.

BACKGROUND: Sleep problems associated with chronic obstructive pulmonary disease may have an important impact on quality of life and health outcome measures in patients. The aim of this study was to prospectively assess differences in symptom profile and polysomnographic parameters in patients with stable mild to moderate COPD and age, gender, and body-mass-index matched controls without airflow obstruction. METHODS: The Sleep Disorders Questionnaire was administered to both patients and controls prior to clinical and polysomnographic evaluation. Responses obtained from the questionnaire were used to construct four independent symptom scales: sleep apnea, periodic limb movement syndrome, psychiatric sleep disorder, and narcolepsy. Associations between each diagnostic scale and sleep parameters were considered by means of multiple analyses of covariance. RESULTS: Fifty-two patients with mild-to-moderate COPD (age 62±8 years, BMI 29±7 kg/sqm) and 52 age, gender, and body-weight matched controls without COPD were studied. Patients with COPD had overall lower sleep efficiency, a lower total sleep time, and lower mean overnight oxygen saturation compared to controls. Patients with COPD were significantly more likely to report symptoms such as insomnia and difficulty in initiating and maintaining sleep, resulting in overall higher psychiatric sleep disorder scale scores in patients compared with controls. Minimum oxygen saturation was an independent predictor for all symptom scales. After correcting for potentially confounding factors, including pack/years of smoking, total sleep time, sleep efficiency, arousal index, mean and minimum oxygen saturation, and apnea-hypopnea-index, the between group-differences for both the periodic limb movement and psychiatric sleep disorder scale scores remained statistically significant. CONCLUSIONS: We observed significant differences in both quantity and quality of sleep between patients with stable mild to moderate chronic obstructive pulmonary disease and respective controls.

Circulating vascular endothelial growth factor and systemic inflammatory markers in patients with stable and exacerbated chronic obstructive pulmonary disease.

The aim of the present study was to assess circulating levels of VEGF (vascular endothelial growth factor), a biomarker with prognostic significance in cardiovascular disease, and markers of systemic inflammation in patients with stable and exacerbated COPD (chronic obstructive pulmonary disease). Lung function parameters, arterial blood gas analysis and circulating levels of VEGF, IL-6 (interleukin-6), TNF-alpha (tumour necrosis factor-alpha), CRP (C-reactive protein), fibrinogen and the peripheral blood neutrophil cell count were assessed in 30 patients on admission to the hospital for acute exacerbation of COPD, in 30 age-, gender- and BMI (body mass index)-matched patients with stable COPD, and 30 matched controls with normal lung function. Patients with acute exacerbated COPD had higher circulating concentrations of VEGF (P<0.001), IL-6 (P<0.05) and CRP (P<0.01) and an increased blood neutrophil cell count (P<0.05) compared with patients with stable COPD and healthy controls. VEGF levels in exacerbated COPD correlated with systemic inflammatory markers, such as CRP (r=0.61, P<0.005), IL-6 (r=0.46; P<0.01) and fibrinogen (r=0.39, P<0.05). In patients with stable COPD, there was a significant relationship between circulating VEGF levels and the percentage of the predicted FEV(1) (forced expiratory volume in 1 s) (r=0.47, P<0.01). Recovery from the exacerbation resulted in a significant decrease in both circulating VEGF levels and markers of systemic inflammation. In conclusion, circulating levels of VEGF and markers of systemic inflammation are up-regulated in patients with acute exacerbated COPD and decrease after recovery from the exacerbation.

Gender-related differences in symptoms of patients with suspected breathing disorders in sleep: a clinical population study using the sleep disorders questionnaire.

BACKGROUND: Gender-related differences in the symptom profile of patients with suspected sleep disordered breathing (SDB) may be one explanation of the clinical underrecognition of SDB in women. STUDY OBJECTIVES: The aim of this study was to prospectively assess gender-related differences in presenting symptoms in a clinical sample of patients with suspected sleep disordered breathing. DESIGN: Administration of the Sleep Disorders Questionnaire prior to clinical and polysomnographic evaluation. Responses obtained from the questionnaire were used to construct 4 independent symptom scales: sleep apnea (SA), periodic limb movement syndrome (PLM), psychiatric sleep disorder (PSY), and narcolepsy (NAR). Analyses of variance were used to examine the effect of gender, AHI, and age on the symptom scales. Associations between gender and each diagnostic scale of the questionnaire were determined by multiple analyses of covariance. SETTING: Tertiary pulmonary referral center. PARTICIPANTS: 2739 men and 782 women with suspected SDB. All patients who were referred to the sleep laboratory underwent full-night polysomnography, irrespective of the likelihood of SDB. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Overall, men scored significantly higher on items related to worsening of snoring/breathing with alcohol (P < 0.001) and smoking history (P < 0.01) than women. Complaints such as witnessed apneas (P < 0.001) and worsening of snoring in supine position (P < 0.05), however, were more frequently reported by men with an apnea-hypopnea index (AHI) < 5/hr, compared with AHI-matched women. There were no significant differences in these items in patients with an AHI > 15/hr. In contrast, women complained significantly more often of insomnia, restless legs, depression, nightmares, palpitations at night, and hallucinations than men. As a result, women had significantly higher scores on the PLM, PSY, and NAR scales of the Sleep Disorders Questionnaire (P < 0.001, for all). After adjustments for age, body mass index, AHI, arousal index, oxygen saturation data, and smoking history, by means of multiple analyses of covariances, gender differences remained significant (P < 0.001, for all scales). CONCLUSIONS: We observed significant gender-related differences in presenting symptoms of patients with sleep disordered breathing at a tertiary level. These differences should be taken into consideration in clinical evaluation of women with suspected sleep disordered breathing.

Bronchoscopy-guided topical hemostatic tamponade therapy for the management of life-threatening hemoptysis.

STUDY OBJECTIVES: Massive hemoptysis is a life-threatening condition. Therapeutic strategies such as interventional angiography, surgery, and/or bronchoscopy have been applied in the clinical setting with variable results. We investigated the efficacy of bronchoscopy-guided topical hemostatic tamponade therapy (THT) using oxidized regenerated cellulose (ORC) mesh in the management of life-threatening hemoptysis. DESIGN: Seventy-six consecutive patients underwent emergency bronchoscopy for massive hemoptysis. Fifty-seven patients (75%) had persistent endobronchial bleeding despite bronchoscopic wedging technique, cold saline solution lavage, and instillation of regional vasoconstrictors. These patients subsequently underwent THT according to the same procedure. SETTING: Teaching hospital, bronchoscopy unit of a 300-bed tertiary pulmonary referral center. RESULTS: THT with ORC was successfully performed on 56 of 57 patients (98%) with an immediate arrest of hemoptysis. All patients successfully treated with THT remained free of hemoptysis for the first 48 h. None required intensive care support or immediate surgery. Mean procedure time (+/- SD) of THT was 11.5 +/- 4.2 min. Recurrence of hemoptysis that was characterized as being mild (< 30 mL) to moderate (30 to 100 mL) developed in six patients (10.5%) 3 to 6 days after THT. Post-obstructive pneumonia developed in five subjects (9%) after endoscopic THT. A subgroup of patients (n = 14) underwent bronchoscopic follow-up 4 weeks after discharge. The ORC mesh was absorbed in all of these patients without signs of foreign body reaction. CONCLUSIONS: Endobronchial THT using ORC is a safe and practicable technique in the management of life-threatening hemoptysis with a high success and a relatively low complication rate.

Spontaneous bilateral diaphragmatic paralysis: a rare cause of respiratory failure.

Bilateral diaphragmatic paralysis (BDP) can occur in the course of motor neuron disease, myopathy, or from mechanical damage or the use of "ice slush" during cardiac surgery. BDP has been observed during and after infections, associated with systemic lupus erythematosus and mediastinal tumors, or may have idiopathic etiology. It is a serious and life-threatening condition. A 62-yr-old man presented with slowly progressive dyspnoea that worsened in the supine position and on bending forward. Chest X-rays, fluoroscopy, lung-function parameters and blood-gas analysis revealed respiratory failure. BDP was confirmed from a phrenic nerve stimulation test and measurement of transdiaphragmatic pressure (Pdi). Since there was no evidence of an obvious etiology, BDP was considered idiopathic. Other muscles were not involved. The pathological basis was probably focal demyelination in segments of the phrenic nerve. Because of increasing diaphragmatic muscle fatigue, the patient was treated with a nasal mask providing bi-level positive airway pressure (BiPAP) ventilation during the night. Clinical suspicion of BDP should always be raised in patients suffering slowly progressive dyspnoea without any obvious cardiac, metabolic or traumatic predisposing factors, and orthopnoea and dyspnoea on bending forward. Electromyographic tests and measurement of Pdi can reveal the correct diagnosis.

A case of primary tularemic pneumonia presenting with necrotizing mediastinal and hilar lymph nodes.

Tularemia is an unusual disease caused by the gram-negative coccobacillus Francisella tularensis. The clinical features of the disease depend on the route of inoculation. Ulceroglandular and typhoidal forms have been recognized as occurring in tularemia, however primary or secondary pneumonic infections have also been reported. Symptoms, laboratory markers and radiological features are non-specific in tularemic pneumonia. Diagnosis is made on clinical grounds and evidence of elevated agglutinating antibodies to F. tularensis (> 1:128). We report a case of primary tularemic pneumonia presenting with pulmonary infiltrates and necrotizing mediastinal and hilar lymph nodes in an otherwise healthy subject from a non-endemic area. Diagnosis of tularemia was obtained serologically, and antibiotic therapy with doxycycline and streptomycin resolved symptoms and radiological abnormalities. We suggest that tularemia should be considered in the differential diagnosis of pneumonia with mediastinal and/or hilar lymphadenopathy.