Vitamin D status in relation to nutritional depletion and muscle function in patients with advanced pulmonary disease.

Muscle weakness is an important complication of advanced pulmonary disease and it is associated with reduced functional activity and lower survival. Vitamin D may be involved in muscle function. The aim of this study was to investigate determinants of calcidiol (25-hydroxycholecalciferol, the major circulating indicator of vitamin D) status and associations between vitamin D metabolites and muscle function in relation to nutritional depletion. Fifty-two percent of the underweight patients (n = 42) and 55% of the normal-weight ones (n = 29) had vitamin D deficiency (< 37.5 nmol/L). The resulting models of linear regression showed that, for the calcidiol model, 24.7% of the variation for calcidiol was explained by fat mass index, vitamin D intake, and FEV(1)/FVC. The results further suggested that vitamin D intake was a stronger predictor of calcidiol status in the underweight patients than in the normal-weight ones. In the resulting models for 6-minute walking distance, calcidiol was a significant predictor, which tended to be more marked in the underweight patients than in the normal-weight ones. Low serum calcidiol concentration was associated with fat mass, lung obstruction, and low intake of vitamin D, especially in the underweight patients, and calcidiol was a predictor of walking distance.

Cytokines, bone turnover markers and weight change in candidates for lung transplantation.

Weight loss in chronic obstructive pulmonary disease (COPD) is associated with increased morbidity and may negatively affect bone mineral density. Increased serum levels of cytokines such as tumour necrosis factor (TNF)-alpha have been associated with weight loss and with bone resorption. We studied the association between systemic inflammation, markers for bone turnover and recent weight change in underweight (n=48) and normal-weight patients (n=23) candidates for lung transplantation where the majority (56%) had COPD. Osteoporosis or osteopenia was present in all the diagnostic groups. The resulting model of linear regression in COPD patients showed that for the 1-CTP (a marker of bone resorption) model, the total variation of 61% was explained by recent weight change, sTNF-alpha receptor(R)II, dose of prednisolon and age. The resulting model of linear regression in the whole group of patients showed that the total variation of 72% was explained by recent weight change, sTNF-alpha RI, diagnosis (COPD/other diagnosis), dose of prednisolon and C-reactive protein. In conclusion, our results showed that serum concentration of 1-CTP was positively associated with sTNF-alpha receptor II and negatively with recent weight change in patients with advanced COPD. Recent weight loss in both the underweight and normal-weight patients showed to be a more important contributor than recent weight loss only in underweight patients for explaining variations in 1-CTP.

[A drooping face; the importance of family history in children with recurrent peripheral facial palsy]. / Een scheef gezicht; het belang van de familieanamnese bij kinderen en jongeren met een recidiverende perifere aangezichtsverlamming.

An 18-year-old girl had experienced drooping at the left corner of the mouth for several weeks and could not close her left eye. These symptoms improved gradually and spontaneously. She had had a similar experience 2 years earlier; at that time, the right side of the face was affected. Family members reported similar episodes. After excluding Lyme borreliosis and cerebellopontine angle tumour, a diagnosis of idiopathic familial peripheral facial palsy was made. Peripheral facial nerve palsy is commonly seen in children and young adults. Obtaining a family history is helpful in these patients: a positive family history is found in 2.4-28.6% of the cases. In the absence of other symptoms, a diagnosis of idiopathic familial peripheral facial palsy should be considered. The prognosis of these patients is generally good and therapy is usually unnecessary.

Possible protection by inhaled budesonide against ischaemic cardiac events in mild COPD.

Epidemiological studies have indicated that chronic obstructive pulmonary disease (COPD) may be associated with an increased incidence of ischaemic cardiac events. The current authors performed a post hoc analysis of the European Respiratory Society's study on Chronic Obstructive Pulmonary Disease (EUROSCOP); a 3-yr, placebo-controlled study of an inhaled corticosteroid budesonide 800 microg.day(-1) in smokers (mean age 52 yrs) with mild COPD. The current study evaluates whether long-term budesonide treatment attenuates the incidence of ischaemic cardiac events, including angina pectoris, myocardial infarction, coronary artery disorder and myocardial ischaemia. Among the 1,175 patients evaluated for safety, 49 (4.2%) patients experienced 60 ischaemic cardiac events. Patients treated with budesonide had a significantly lower incidence of ischaemic cardiac events (18 out of 593; 3.0%) than those receiving placebo (31 out of 582; 5.3%). The results of the present study support the hypothesis that treatment with inhaled budesonide reduces ischaemic cardiac events in patients with mild chronic obstructive pulmonary disease.

Genetic and environmental effects on exhaled nitric oxide and airway responsiveness in a population-based sample of twins.

Elevated levels of exhaled nitric oxide (eNO) and airway hyperresponsiveness are intermediate phenotypes of asthma. Using population-based data collected from a sample of twins, the present authors estimated the relative contribution of genes, family environment and nonshared environmental influences to variations in eNO and airway responsiveness (AR). In addition, the genetic and environmental sources of covariation between these two asthma-related phenotypes were investigated. The study population comprised a random sample of 377 adult twins identified through the Norwegian Twin Registry. The main outcome variables were eNO and AR to methacholine. Genetic effects accounted for 60% of the variation in eNO. Family environment accounted for 30% of the variation in AR, while nonshared environmental influences explained the remaining variation for both measures. For both eNO and AR, there were significant regression effects for atopy and smoking. The small, but significant association between eNO and AR was primarily explained by genetic factors. Sub-analyses restricted to atopic and nonsmoking twins strengthened the observation. In conclusion, variations in exhaled nitric oxide and airway responsiveness appear to be explained by different genetic and environmental variance structures. Variation in exhaled nitric oxide is explained by genetic and nonshared environmental effects, whereas an environmental model best explains the variation in airway responsiveness. Common genetic effects explain the small but significant association between exhaled nitric oxide and airway responsiveness.

Inflammatory markers in bronchoalveolar lavage fluid from human volunteers 2 hours after hydrogen fluoride exposure.

Fluoride has been in focus as a possible causal agent for respiratory symptoms amongst aluminium potroom workers for several decades. Previously, using bronchoalveolar lavage (BAL), we demonstrated airway inflammation in healthy volunteers 24 hours after exposure to hydrogen fluoride (HF). The objective of the present study was to examine early lung responses to HF exposure. Bronchoscopy with BAL was performed 2 hours after the end of 1-hour exposure to HE Significant reductions in the total cell number and the number of neutrophils and lymphocytes were observed in bronchoalveolar portion (BAP), whereas there were no significant changes in the bronchial portion (BP). Significantly decreased concentrations of beta2-MG, IL-6 and total protein were found in both BAP and BP. Additionally, IL-8 was significantly reduced in BP, and ICAM-1 and albumin were present in lower concentrations in BAP. Lung function measurements were not affected by HF exposure. These reported effects are presumably transitory, as many were not present in the airways 24 hours after a similar HF exposure.

Lung function 5 yrs after allogeneic bone marrow transplantation conditioned with busulphan and cyclophosphamide.

Long-term data on lung function after bone marrow transplantation (BMT) are inconclusive. Previously, a persistent reduction in gas transfer 1 yr after allogeneic BMT with busulphan and cyclophosphamide conditioning was reported by the current authors. In the present study this reduction was examined to see if it was permanent, transient or progressive. Prospectively, 43 consecutive adult patients with malignant blood disorders undertook lung function measurements prior to BMT, at 3 month intervals during the 1st yr after BMT and finally after 5 yrs. Mean baseline lung function values were >90% predicted. Within the 1st yr after BMT a transient decline in lung volumes and a persistent reduction in gas transfer were observed. After 5 yrs, baseline values were restored for all variables, except in four patients who developed obliterative bronchiolitis. Acute leukaemia and smoking were independently associated with gas transfer reductions at baseline and during the 1st yr after BMT. Allogeneic bone marrow transplantation with busulphan and cyclophosphamide conditioning was associated with a reduction in gas transfer 1 yr after bone marrow transplantation but baseline values were usually restored after 5 yrs. Since recovery may be gradual and slow, an observation period >1 yr is required before drawing conclusions concerning the development of a permanent reduction in lung function after allogeneic bone marrow transplantation conditioned with busulphan and cyclophosphamide.

Vitamin D deficiency, bone mineral density and weight in patients with advanced pulmonary disease.

OBJECTIVE: To study the influence of underweight, body composition and vitamin D deficiency on bone mineral density in patients with advanced pulmonary disease. DESIGN: Cross-sectional study with time span for inclusion set at 5 years. SETTING: The clinical work and biochemical analyses were carried out at Rikshospitalet University Hospital, Norway. Analyses for vitamin D metabolites and bone markers were carried out at Aker University Hospital, and bone measurements at Clinic of Osteoporosis. SUBJECTS: Seventy-one candidates for lung transplantation (63% chronic obstructive pulmonary disease, 42 underweight and 29 normal weight) were included. MAIN OUTCOME MEASURES: Body composition, bone mineral density at lumbar spine and femur neck, serum concentration of calcidiol and vitamin D intake. RESULTS: Subnormal calcidiol levels were present in 52% of the underweight patients and 69% of the normal-weight patients. The resulting models of linear regression showed that for the lumbar spine T scores model, the total variation of 16.7% was explained by group (underweight/normal weight), sex and age. For the femur neck T scores model, the total variation of 20.4% was explained by the interaction of underweight and vitamin D deficiency (with borderline significance) and by arm muscle circumference percentage of standard. In patients with normal calcidiol levels, the median intake of vitamin D was 17 microg in the underweight patients and 11 microg in the normal-weight patients. CONCLUSIONS: Vitamin D deficiency was common in both underweight and normal-weight patients, but only in the underweight patients, an association between vitamin D deficiency and reduced femur neck T scores was indicated.

Human exposure to hydrogen fluoride induces acute neutrophilic, eicosanoid, and antioxidant changes in nasal lavage fluid.

The development of asthmalike symptoms among aluminum potroom workers has been associated with exposure to fluorides. In the present study, the immediate nasal response in humans was examined subsequent to short-term hydrogen fluoride (HF) exposure. Ten healthy subjects were exposed to HF (3.3-3.9 mg/m(3)) for 1 h. Nasal lavage (NAL) was performed before, immediately after, and 1.5 h after the end of exposure. Control lavages were performed on the same subjects at the same time points but without HF exposure. At the end of HF exposure, 7 of 10 individuals reported upper airway symptoms. A significant increase was observed in the number of neutrophils and total cells, while there was a decrease in cell viability. The changes in neutrophil numbers correlated significantly with the reported airway symptoms. HF also induced a significant increase in tumor necrosis factor-alpha and the total protein content of NAL fluid. Among the eicosanoids, prostaglandin E(2), leukotriene B(4), and peptide leukotrienes were elevated after exposure. Of the antioxidants measured, the concentration of uric acid increased after exposure. In conclusion, exposure to HF induced immediate nasal inflammatory and antioxidant responses in healthy human volunteers. These findings may contribute to a further understanding of the way HF exerts damage to the airways and show that HF could represent an occupational hazard.

A study of intensified dietary support in underweight candidates for lung transplantation.

BACKGROUND: No data is available on dietary intervention in candidates for lung transplantation and on the effect of different strategies for dietary support in this cohort. AIM: We therefore wanted to evaluate the effects of intensified nutritional support compared with simple support on energy intake and nutritional status. METHOD: Our participants were underweight (n = 42) and normal-weight (control group, n = 29) candidates for lung transplantation. The underweight patients were randomized into two groups. Group A received intensified dietary counselling, ready-made liquid nutritional supplements free of charge and regular follow-ups, while group B received only one session of individual dietary counselling, no supplements and no follow-ups. RESULTS: The mean intervention time was 21 weeks. Groups A and B both increased their energy intake and gained weight. Group A increased their energy intake from a median of 8.7 to 10.1 MJ (p < 0.01 compared with the control group after intervention) and gained a mean of 2.9 kg body weight (95% CI 1.2; 4.7, p = 0.005 compared with the control group), while group B increased from 7.4 to 10.8 MJ (p = 0.005) and gained 2.3 kg (1.2; 3.3, p = 0.002). Only group B increased their fat-free mass. In this group, an increase in O(2) saturation and a decrease in PaCO(2) were suggested. None of the groups improved its physical performance. CONCLUSION: In candidates for lung transplantation we were unable to confirm the hypothesis that intensified nutritional support compared with a simple support increased compliance. Both groups achieved the goal for energy intake and gained weight.

Gas and dust exposure in underground construction is associated with signs of airway inflammation.

Exposure to gases and dust may induce airway inflammation. It was hypothesized that heavy construction workers who had been exposed to dust and gases in underground construction work for 1 yr, would have early signs of upper and lower airway inflammation, as compared to outdoor workers. A study group comprising 29 nonsmoking underground concrete workers (mean +/- SD age 44+/-12 yrs), and a reference group of 26 outdoor concrete workers (39+/-12 yrs) were examined by acoustic rhinometry, nasal and exhaled nitric oxide spirometry and a questionnaire on respiratory symptoms. Exposure measurements were carried out. The underground workers had higher exposure to total and respirable dust, alpha-quartz and nitrogen dioxide than the references (p<0.001). The occurrence of respiratory symptoms was higher in the underground workers than in the references (p<0.05). Exhaled nitric oxide (NO) (geometric mean+/-SEM) was higher in the underground workers than in the references (8.4+/-1.09 versus 5.6+/-1.07 parts per billion (ppb), p = 0.001), whereas spirometric values were comparable. The underground workers had smaller nasal cross-sectional area and volume than the references, and more pronounced increases after decongestion (p<0.001). To conclude the exposure in underground construction may cause nasal mucosal swelling and increased levels of exhaled nitric oxide, indicating signs of upper and lower airway inflammation.

Dietary support to underweight patients with end-stage pulmonary disease assessed for lung transplantation.

BACKGROUND: Undernutrition in hospitalized patients is often not recognized and nutritional support neglected. Chronic obstructive pulmonary disease is frequently characterized by weight loss. No data exist on the effects of nutritional supplementation in underweight lung transplantation candidates during hospitalization. OBJECTIVE: To evaluate the effects on energy intake and body weight of an intensified nutritional support compared to the regular support during hospitalization. METHODS: The participants were underweight (n = 42) and normal-weight (n = 29) patients with end-stage pulmonary disease assessed for lung transplantation. The underweight patients were randomized to receive either an energy-rich diet planned for 10 MJ/day and 45-50 energy percentage fat and offered supplements (group 1), or the normal hospital diet planned for 8.5-9 MJ/day and 30-35 energy percentage fat and regular support (group 2, control group). The normal-weight control patients (group 3) received the normal diet. Food intake was recorded for 3 days. RESULTS: During a mean hospital stay of 12 days, the energy intake was significantly greater for the patients on intensified nutritional support (median 11.2 MJ) than for the underweight patients on the regular support (8.4 MJ; p < 0.02) and the normal-weight patients (7.0 MJ; p < 0.001). The increase in energy intake in group 1 resulted in a significant weight gain (median 1.2 kg) compared with group 2 (p < 0.01) and group 3 (p < 0.001). CONCLUSIONS: In a group of underweight patients with lung disease assessed for lung transplantation, it was possible to increase energy intake by an intensified nutritional support which was associated with a significant weight gain, compared to the regular nutritional support during a short hospital stay.

Serum amino acids in relation to nutritional status, lung function and energy intake in patients with advanced pulmonary disease.

Malnutrition, hypoxia and energy deficit may affect protein metabolism. We wanted to evaluate the cross-sectional association between serum amino acids and fat-free mass in a group of hypoxic patients. We also wanted to explore, in the same group of patients, whether the blood amino-acid pattern could possibly be influenced by differences in lung function and energy intake. Serum amino acids were measured in 71 hypoxic underweight and normal-weight patients with advanced pulmonary disease and related to the fat-free-mass index, arterial oxygen (PaO2) and carbon dioxide tension (PaCO2), forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1) and energy intake. Only one amino acid (aspartic acid) remained significantly correlated to the fat-free-mass index after adjustments for age and sex (beta = -0.30, P=0.011). None of the amino acids were significantly correlated to PaO2 but alanine was significantly negatively correlated to PaCO2 (beta = -0.46, P<0.001), phenylalanine to FVC1 (beta = 0.52, P=0.001) and tyrosine to FVC (beta = 0.36, P=0.008). Citrulline and tryptophan were significantly correlated to energy intake (beta = 0.32, P=0.008; beta=0.37, P=0.009 respectively). In conclusion, there was no convincing association between fat free mass and serum amino acids. The negative effect of hypercapnia and reduced lung function on some serum amino acids was suggested and some amino acids were sensitive to reduced energy intake.

Health-related quality of life is associated with arterial P(O2) in chronic obstructive pulmonary disease.

Insensitive lung-specific questionnaires may explain the poor association between arterial P(O2) and reported health-related quality of life. Conceivably, modern lung specific or generic quality of life measures might show a better association with arterial P(O2). Fifty-nine outpatients (34 men) with chronic obstructive pulmonary disease (COPD) who fulfilled the following criteria were studied: age 18-67 years, FEV1 < or = 70%, < or = 15% reversibility after beta2-agonist inhalation, and no other disabling disorders. All completed the Respiratory Quality of Life Questionnaire (RQLQ) and Short Form 36 (SF-36), and were tested with spirometry and arterial blood gases. In accordance with available COPD staging systems, patients were divided into those with an FEV1 of < 50% and 50-70% of predicted. Patients' characteristics were, [mean (SD)]: age: 57.0 years (9.0); FEV1: 1.46 (0.6). Spearman's rank correlations between arterial P(O2) and dimensions of the RQLQ ranged from 0.25-0.52, and were greater than for the SF-36 (0.14-0.36) in patients with moderate to severe COPD. The association between arterial P(O2) and quality of life scores in moderately to severely affected COPD patients was moderate, but higher than previously reported. The associations were higher with a lung-specific questionnaire than with a general health measure, indicating a higher sensitivity of the lung-specific measure in this patient group.

Health-related quality of life in lung transplant candidates and recipients.

BACKGROUND: Studies on the health-related quality of life in lung transplantation have used general questionnaires, although lung-specific instruments might be more sensitive to small differences. OBJECTIVES: To compare the health-related quality of life of lung transplant recipients with lung transplant candidates, using lung-specific and general instruments, and to assess the reliability and validity of these questionnaires. METHODS: The study is a cross-sectional postal survey of 31 lung transplant recipients and 15 candidates, using the following outcome measures: St. George's Respiratory Questionnaire (SGRQ), a lung-specific health status instrument; the Short Form 36 (SF-36), a general measure, and the Hospital Anxiety and Depression scale (HAD). RESULTS: The SGRQ showed a significantly better score (p < 0.05) for transplant recipients in the impacts and activity dimensions and the total score than for candidates. SF-36 scores showed a similar improvement in all subscales of the SF-36 except bodily pain. Cronbach's alpha for all dimensions of the SGRQ, SF-36, and HAD were 0.77-0.95. CONCLUSIONS: Patients surviving lung transplantations can expect a considerable improvement in most dimensions of health-related quality of life. This finding was consistent using both lung-specific and general measures. The reliability of the questionnaires was acceptable. The associations between scales support the validity of the questionnaires in this setting.

Health status, dyspnea, lung function and exercise capacity in patients with chronic obstructive pulmonary disease.

SETTING: A secondary hospital outside Oslo. OBJECTIVE: To assess relationships between health status and measures of dyspnea, lung function and exercise capacity in patients with chronic obstructive pulmonary disease (COPD), to identify dimensions where lung-specific instruments associate and discriminate better than general measures. DESIGN: We assessed health status in 59 out-patients with COPD, using the following instruments: Short Form 36 (SF-36)-a general health status measure, Respiratory Quality of Life Questionnaire (RQLQ)-a lung-specific measure, the Karnofsky performance scale, and a rating scale. All patients rated their dyspnea and had spirometry and exercise capacity measured. RESULTS: Mean (SD) patient age was 57.3 (9.7) years, FEV1 47% (15%) of predicted, 6 minute walk distance 503 m (122 m). Dyspnea was the strongest predictor for health status. Both SF-36 and RQLQ had dimensions associating well with dyspnea and exercise capacity. The associations with FEV1 ranged from none to moderate. CONCLUSION: All RQLQ scales had a moderate to substantial association with indices of dyspnea and exercise capacity, while the SF-36 associated well only in dimensions related to physical health. The general measure has a broader scope and complements the lung-specific measure. These findings support the construct validity of both the SF-36 and the RQLQ, and justify using a general measure to supplement a lung-specific measure.

Increased CD3 positive cells in bronchoalveolar lavage fluid after hydrogen fluoride inhalation.

OBJECTIVES: This study examined whether experimental hydrogen fluoride exposure for 1 hour induces an inflammatory response in the lower respiratory tract that is detectable in bronchoalveolar lavage fluid. METHODS: Nineteen healthy, nonsmoking men were exposed for 1 hour to constant low (<0.6 mg/m3), intermediate (0.7-2.4 mg/m3), or high (2.5-5.2 mg/m3) concentrations of hydrogen fluoride. Bronchoalveolar lavage was performed at least 3 weeks before and 24 hours after the exposure. For 15 subjects differential countings were performed. RESULTS: There was a significant increase in the percentage of CD3 positive cells in the bronchial portion for those exposed to "intermediate" and "high" concentrations. For the "high" exposure group the increase in the bronchoalveolar portion was also significant. A significant correlation was found between the increase in the percentage of lymphocytes and CD3 positive cells in the bronchoalveolar portion (Spearman's coefficient r=0.68, P=0.008). Myeloperoxidase and interleukin-6 increased significantly in the bronchial portion for those exposed to "high" concentrations. There was a significant increase in myeloperoxidase (P=0.005) for all the exposures, while there was a decrease in E-selectin (P=0.007). CONCLUSIONS: Hydrogen fluoride may induce an inflammatory reaction in the airways at concentrations that can occur in the ambient air in the primary aluminum industry.