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.

[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.

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.

Chest radiograph--a poor method for determining the size of a pneumothorax.

The ability of chest radiographs to determine the size of a pneumothorax was tested in 16 patients using computed tomographic (CT) scan as a reference method. To determine if CT with a slice thickness of 12 mm could be used, its accuracy was assessed in a lung model experiment. The lung model consisted of a water-filled plastic bag (lung) fitted into a plastic chamber (hemithorax), both of approximately the same size and shape as in man. Water was drawn off in incremental steps and a CT was done after each step. The area of the pneumothorax was calculated by computer and when multiplied by slice thickness and number of slices, the total volume of the pneumothorax could be compared with the extracted amount of water. A good correlation (r = 0.99), with the line of regression close to the line of identity, was found between the CT investigation and the artificial pneumothorax. In the patients, the size of the pneumothorax, judged by radiograph using two different methods of calculation, was correlated to the size obtained by CT. The correlation was poor (r = 0.71) irrespective of method of calculation. The size of the pneumothorax estimated by CT showed a good correlation (r = 0.99) to the initial aspirated air volumes in 12 of the 16 patients treated with drainage. A cautious attitude toward the use of chest radiographs for calculations of the degree of lung collapse in patients with pneumothorax is recommended.

Postnatal maternal smoking increases the prevalence of asthma but not of bronchial hyperresponsiveness or atopy in their children.

We have compared the prevalence of asthma, bronchial hyperresponsiveness (BHR), and atopy in relation to parental smoking in children aged 7 to 13 years. Information on the presence of asthma was obtained from a questionnaire, BHR was assessed by a methacholine challenge test, and atopy was defined as a positive response to a skin prick test. A complete history of the parents' smoking habits during their children's life, including prenatal smoking habits, was recorded. The prevalence of maternal smoking increased from 37.9% during pregnancy to 45.3% at the cross-sectional survey. None of the outcomes was significantly related to paternal smoking, whereas postnatal maternal smoking was positively associated with asthma (odds ratio [OR] = 2.8; 95% confidence interval [CI], 1.3 to 6.1). A negative association between prenatal maternal smoking and atopy was found (OR = 0.6; 95% CI, 0.3 to 0.9). We found no significant association between BHR and parental smoking. Our results indicate that postnatal maternal smoking increases the prevalence of asthma in the offspring without inducing BHR.

Survival of patients with severe thoracic spine deformities receiving domiciliary oxygen therapy.

Scoliosis can lead to respiratory failure and premature death. Alveolar hypoventilation is a dominant cause and artificial ventilation at home (AVH) is probably the treatment of choice. It has been suggested that long-term domiciliary oxygen therapy (LTO) is of little value because of the worsening of hypercapnia. We analyzed survival and predictors of death among 80 patients with scoliosis and other severe thoracic spine deformities receiving LTO for chronic hypoxia. The survival rate was higher in patients under the age of 65 (p = 0.01) and in patients without concomitant pulmonary or airways disease. Likewise, the survival rate was higher in patients with a PaCO2 of greater than 7.4 kPa than in patients with a lesser degree of hypoventilation and hypercapnia (p less than 0.05). The risk of developing life-threatening hypercapnia during well-controlled LTO appeared to be small. In younger patients without complicating disease, long-term survival was achieved with LTO, but with time, an increasing proportion of the patients changed to AVH, with or without LTO.

Single lung transplantation as treatment for end-stage pulmonary sarcoidosis: recurrence of sarcoidosis in two different lung allografts in one patient.

Three patients have undergone single lung transplantation in our hospital because of respiratory failure as a result of sarcoidosis. Two patients survived the postoperative period. Obliterative bronchiolitis developed in one of these patients, and recurrence of sarcoidosis in the transplanted lung necessitated contralateral single lung transplantation. Nine months later the first transplant became necrotic and infected and had to be removed. The postoperative course was uncomplicated. However, transbronchial biopsy specimens 10 months after retransplantation show sarcoid changes also in the second transplant, but without any signs of cellular rejection.

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.

Study of pH and temperature-induced transitions in urate oxidase (Uox-EC1.7.3.3) by microcalorimetry (DSC), size exclusion chromatography (SEC) and enzymatic activity experiments.

Purified recombinant urate oxidase (urate oxygen oxidoreductase EC 1.7.3.3. re-Uox) has been studied by means of differential scanning calorimetry (DSC) in correlation with enzymatic activity measurements and size exclusion chromatography. Differential scanning calorimetry curves versus pH show two endothermal effects in the pH range 6-10. The first endotherm reveals a maximum stability between pH 7.25 and pH 9.5 corresponding to a temperature of transition T(m1) of 49.0 degrees C and an enthalpy of transition of 326 kJ mol(-1). This value dramatically decreases below pH 7.25. The behavior of the second endotherm is more complex but the temperature of transition T(m2) is constant between pH 9 and 7.25 and a maximum for the corresponding enthalpy is obtained near pH 8 with DeltaH(2)=272 kJ mol(-1). An optimal pH of 8.0 for the stability of the enzymatic activity at elevated temperature was also found which was in good agreement with calorimetric results. Reversibility of the first endotherm is obtained from 20 to 51.5 degrees C. The calorimetric result is correlated to enzymatic activity, purity by size exclusion chromatography (SEC) and protein concentration measurements. In contrast, for the second endotherm, after heating up to 68.9 degrees C, no reversibility was found. Interaction with structural analogues of urate has been studied by DSC. 8-Azahyooxanthine has only a small effect and caffeine has no effect at all. With 8-azaxanthine, a rapid increase of the T(m1) function of the concentration is obtained. At high concentration T(m1) reached the T(m2) value which remained unaffected.

Performance of a short lung-specific health status measure in outpatients with chronic obstructive pulmonary disease.

The objective of this study was to assess the performance of a lung-specific health status measure in patients with chronic obstructive pulmonary disease (COPD). We used the Respiratory Quality of Life Questionnaire (RQLQ), a modification of an Australian questionnaire intended for asthma patients and adapted in this study to fit patients with COPD also. For comparison we chose the general health profile measure Short Form 36 (SF-36). We assessed the five RQLQ scales and eight SF-36 scales for reliability, validity and responsiveness in 59 outpatients attending a Norwegian hospital for COPD. Statistical analysis included internal consistency, test-retest reliability and convergent validity between the two questionnaires. Responsiveness was assessed in patients reporting global change in health status over 1 year. All scales of the RQLQ showed good internal consistency (Cronbach's a = 0.85-0.94) and test-retest reliability (intraclass correlation coefficient = 0.86-0.94), as did the SF-36 scales (a = 0.66-0.90) and intraclass correlation coefficient = 0.60-0.86). Pearson correlations between scales with similar items ranged from 0.54 to 0.76, supporting the construct validity of both questionnaires. The RQLQ had responsive scales, showing significant changes in the expected direction over 1 year. We conclude that the RQLQ showed an acceptable reliability, construct validity and responsiveness in COPD patients, encouraging further use of this questionnaire.

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.

Do patients using long-term liquid oxygen differ from those on traditional treatment with oxygen concentrators and/or compressed gas cylinders? A comparison of two national registers.

Long-term oxygen therapy (LTOT) in patients with chronic hypoxaemia is an expanding field. Traditional stationary oxygen, with and without portable compressed gas cylinders, and portable liquid oxygen equipment is available today. No official guidelines exist for the prescription of liquid oxygen vs traditional oxygen supply in LTOT, although it is generally though that patients receiving liquid oxygen are younger and less seriously affected. The authors tested this hypothesis by comparing register data from two national Scandinavian registers of patients on LTOT in the same time period; one including all the patients on traditional oxygen treatment alone, e.g. concentrators and compressed gas cylinders (n = 1039), the other including all the patients using portable liquid oxygen alone (n = 117). About 80% of the patients in both groups suffered from chrome obstructive pulmonary disease. Younger patients were found in the liquid oxygen group (P < 0.004), but with clinically slightly worse blood gas derangement (mostly statistically significant). They had higher frequency of previous or present oedema (P < 0.0001), and there were more smokers in this group (P < 0.0001). No significant differences were seen with respect to sex distribution or oxygen delivery systems. Higher oxygen dose and longer daily oxygen treatment (P < 0.0001) were prescribed for the liquid oxygen patients compared with the patients on traditional oxygen with statistically higher oxygen tension during the prescribed treatment. A slight further increase in PaCO2 was seen in both groups during oxygen treatment, of doubtful significance. Compared with patients on traditional oxygen, liquid oxygen thus appears to be prescribed for younger patients, independent of clinical status or blood gas levels.

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.

Single lung transplantation for chronic obstructive pulmonary disease: pulmonary function and impact of bronchiolitis obliterans syndrome.

Chronic obstructive pulmonary disease (COPD) is now the most common indication for single lung transplantation. In long-term follow-up, obliterative bronchiolitis is a major problem. The aim of the present study was to perform a long-term follow-up of the pulmonary function and to examine the effect of development of bronchiolitis obliterans syndrome (BOS). Nineteen patients with end-stage COPD underwent single lung transplantation and were followed regularly with pulmonary function tests, and ventilation and perfusion scintigraphy (mean observation time 29 months). They were divided into two categories, with and without BOS, using the definition recommended by the International Society for Heart and Lung Transplantation working group. A mixed model analysis of variance with BOS as co-variate was used to evaluate its effect on pulmonary function. Spirometry, lung transfer factor for carbon monoxide (TLCO), arterial blood gases and 6-min walk test improved significantly (P < 0.001) from before transplantation to 3 months after transplantation. Nine patients developed BOS. Implied by the definition of the syndrome, forced expiratory volume in 1 s (FEV1) was significantly (P < 0.001) lower for patients with BOS while there was no significant effect of BOS category on TLCO corrected for alveolar volume (VA) or perfusion to transplant. Patients without BOS maintained their pulmonary function, and ventilation and perfusion to transplant for more than 3 yr after transplantation. The present results suggest that decreasing FEV1 accompanied by an unchanged TLCO/VA and pulmonary perfusion support the diagnosis of BOS after single lung transplantation for COPD.

Beta 2-agonists administered by a dry powder inhaler can be used in acute asthma.

Patients with acute asthma attending the emergency room were included in a double-blind, double-dummy and parallel group study to investigate whether a dry powder inhaler (Turbuhaler) can be used in acute asthma. If so, the aim was to establish the potency relationship between a beta 2-agonist (salbutamol) administered by the dry powder inhaler and the pressurized metered-dose inhaler (pMDI). Eighty-six patients with a mean age of 38 years and forced expiratory volume in 1 s (FEV1) of 37% of predicted normal value were randomized at Siriraj Hospital in Bangkok to either Turbuhaler (50 micrograms dose -1) or pMDI (100 micrograms dose -1) with spacer (Volumatic). Doses of 100 + 300 + 300 + 300 micrograms salbutamol were given at 0, 15, 30 and 45 min via Turbuhaler and repeated at 90, 105, 120 and 135 min (total dose 2000 micrograms). The same inhalation schedule with identical number of doses was used for the pMDI with spacer but in double doses (total 4000 micrograms), assuming a dose-potency ratio of salbutamol administered via Turbuhaler compared with the pMDI of 2:1. At 85 min after the first dose, 60 mg prednisolone was given orally. FEV1 was measured 10 min after each dosing. Peak inspiratory flow (PIF) through Turbuhaler was measured on each dosing occasion. Plasma (P)-salbutamol, serum (S)-potassium concentrations, pulse rate, blood pressure and adverse events were recorded. No statistically significant differences were observed in the increase in FEV1 between the groups: 55 min (165 min) after the first dose, the increase was 0.47 l and 47% (0.64 l and 63%) in the Turbuhaler group, and 0.46 l and 42% (0.68 l and 65%) in the pMDI group. Mean PIF though Turbuhaler was 49 l min -1 (range 26-68) at first inhalation and increased to 60 l min -1 (range 38-86). There was no correlation between the initial PIF through Turbuhaler and the initial FEV1 response. P-salbutamol and S-potassium values correlated well. A larger decrease in S-potassium was noticed after 75 min in the pMDI group (0.38 mmol l -1) compared with the Turbuhaler group (0.23 mmol l -1) (P = 0.02). In conclusion, the use of a dry powder inhaler, Turbuhaler, was investigated in the emergency room treatment of acute asthma, and was as effective as a pMDI with spacer. Half the dose of salbutamol administered via Turbuhaler was as effective as the full dose given via a pMDI with spacer.

Increased variability in bronchial responsiveness in aluminum potroom workers with work-related asthma-like symptoms.

In a longitudinal study, we studied the variability in bronchial responsiveness (BR) to methacholine in aluminum potroom workers suffering from work-related asthma-like symptoms (WASTH) and in symptom-free workers. In the index group, 26 men suffering from WASTH were selected from a cross-sectional survey. The reference group comprised 45 symptom-free men recruited from the enrollment of new employees. Bronchial responsiveness was expressed as the dose-response slope (DRS) of the line through origin and the last data point. The standard deviation of the log-transformed DRS was positively associated with symptom score (P = .012) and the mean BR (P < .001). Our results indicate that the severity of respiratory symptoms in aluminum potroom workers with WASTH reflects the variability in BR.

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.

The use of isolated lung cells in in vitro pulmonary toxicology: studies of DNA damage, apoptosis and alteration of gene expression.

Isolated lung cells constitute a valuable system for studying mechanisms involved in chemically induced toxicity in the lung. Different lung cells isolated from various species may be studied. Bronchiolar Clara and alveolar type 2 cells produce important lung-specific proteins, hold a major role in the metabolism of xenobiotics and serve as progenitor cells for other lung cell types. They are possible target cells in lung carcinogenesis. Alveolar macrophages play an important role in lung defence and in inflammatory responses. In the present study we have characterised chemically induced DNA damage, apoptosis, changes in cell cycle progression, transformation and alterations in gene expression in these specific lung cells isolated from rat, rabbit and human. Major differences between the cell types and the various species in the induction of DNA damage by chemicals were found, as measured by the 32P-postlabelling and alkaline filter elution techniques. Benzo(a)pyrene and hydrogen fluoride were found to induce apoptosis in the isolated cells as measured by microscopical analysis and flow cytometry. The function of various important tissue- or cell type specific proteins (CYP 2B1, Clara cell protein) and/or cellular signal transduction pathways constitute important targets that may be affected by exposure to toxic compounds. Using immunological and molecular techniques the differential expression of specific proteins/RNAs and their activity can be studied. Among other proteins, c/ebp is involved in the regulation of transcription at the end of signal pathways. The protein is differentially expressed in rat lung cells and thus could be suitable for studying differential toxic effects in various lung cells. In humans, bronchoalveolar lavage (BAL) fluid from human volunteers can be readily obtained and examined after exposure to different chemical compounds. An increase in the percentage of CD3-positive cells (T-lymphocytes) was found after exposure to hydrogen fluoride. The number of certain cell types and cytokines may be used to estimate the degree of inflammatory reaction. In conclusion, the use of in vitro data including the use of specific, primary human lung cell types may contribute considerably to the quality of risk assessment, together with in vivo data from animals and man.

[An answer to an inquiry on diffuse panbronchiolitis. Now it has found its way here!]. / Svar på efterlysning av diffus panbronkiolit. Nu har den hittat hit!

Diffuse panbronchiolitis (DPB) is a disease characterised by chronic inflammation in the region of respiratory bronchioles. The condition has mainly been observed in Japanese patients, though isolated cases have been reported from other countries. In a review published in Läkartidningen (37/94), the question was raised of why this disease had not been seen in Scandinavia, and whether this might be the result of missed diagnosis. The diagnostic criteria were listed, and the question was posed of whether (Scandinavian) physicians existed who had encountered patients with chronic sinusitis, persistent cough and inexplicable nodular changes in lung x-rays. As a direct result of this enquiry, the present article reports what may well be the first Scandinavian patient to fulfil all the diagnostic criteria of DPB. The patient responded with improved lung function and normalised blood gases to a combined treatment regimen comprising immunosuppression (cyclophosphamide and prednisolone) and nebulised antibiotics (gentamicin).