Hans Hedenström

Reference Values for Lung Function Tests in Men: Regression Equations with Smoking Variables

Prediction formulas for static and dynamic spirometry, gas distribution, static lung mechanics and the transfer test were derived from measurements in healthy men. The measurements included total lung capacity, residual volume, airways resistance, static elastic recoil pressure of the lung, static compliance, closing volume, slope of the alveolar plateau (phase III), flow-volume variables (including mean transit time) during breathing of air or a helium/oxygen mixture, and conventional spirometric indices. The results from 146 smokers and 124 never-smokers were evaluated separately and combined. For all lung function tests a single regression equation was obtained. The prediction formulas included time-related smoking variables and were valid for both smokers and never-smokers. For many lung function tests, a nonlinear age coefficient resulted in a significant reduction in variance compared with simple linear models. Heavy tobacco smoking influenced most lung function tests less than ageing from 20 to 70 years, but for airways resistance, transfer factor and phase III the opposite was found.

Pulmonary function after autologous bone marrow transplantation in children: a long-term prospective study.

Summary:We performed serial pulmonary function tests (PFTs) consisting of spirometry and diffusing capacity in 26 children after BMT. The median follow-up was 10 years. The influence of total body irradiation (TBI) on long-term pulmonary function was of particular interest. In the 20 children who had received TBI, after an initial decrease the PFTs showed recovery, but the mean lung volumes were still significantly decreased 5 years after BMT at 10% below baseline. The proportions of children with restrictive impairment 5 and 10 years after BMT were 20 and 21%, respectively. Only one child was diagnosed with obstructive impairment. The proportions of children with isolated diffusing impairment at 5 and 10 years were 7/20 (35%) and 7/13 (54%), respectively. Six children had received chemotherapy only and showed isolated diffusing impairment as the only long-term sequela in 4/5 and 1/3 at 5 and 10 years. Our main finding was that there was little change in PFTs 1–10 years after BMT. TBI was associated with persistently decreased lung volumes in a proportion of patients, whereas chemotherapy also might have been of importance for the development of impaired gas exchange.

Exhaled nitric oxide and its relationship to airway responsiveness and atopy in asthma

Abstract Exhaled nitric oxide (NO) has attracted increasing interest as a non-invasive marker of airway inflammation. The purpose of this study was to determine whether exhaled nitric oxide in subjects with asthma varied according to their atopic status and to examine its correlation with airway hyperresponsiveness and lung function measurements. Forty patients with asthma and 13 controls participated in the study. Nitric oxide was measured on three occasions with intervals of at least 3 days, using a chemiluminescence method. Airway responsiveness was assessed with methacholine challenge and lung function measurements were made. All subjects recorded peak expiratory flow and kept a symptom diary during a 17-day period. There was no significant difference in lung function measurements, peak expiratory flow or symptom score between the two asthma groups. Atopic patients with asthma had a significantly higher mean amount of exhaled NO than non-atopic subjects with asthma (162 ± 68 vs. 113 ± 55 nl min −1 ; P = 0·03) and the control group (88 ± 52 nl min −1 ; P = 0·004). No significant difference was found in the amount of exhaled NO between non-atopic patients with asthma and the controls. In atopic subjects with asthma the mean exhaled NO was significantly correlated to the dose-response slope for methacholine ( r = −0·52; P = 0·02), while no such correlation was found in the non-atopic group. In conclusion; in this study, atopic subjects with asthma had higher levels of exhaled NO than non-atopic subjects. Atopic status should be taken into account when measuring levels of exhaled NO in subjects with asthma.

Investigation of the Excluded Stomach after Roux-en-Y Gastric Bypass

Background: One problem with Roux-en-Y gastric bypass (RYGBP) is that it leaves the bypassed segment not readily available for endoscopic or radiographic examinations. Materials and Methods:Three males, 50, 54 and 64 years old, suffered from repeated, gastrointestinal bleeding of unknown origin requiring transfusion 1/2, 1 and 7 years after RYGBP. Access to the stomach was obtained by an ultrasound-guided percutaneous gastrostomy. Results: We could perform endoscopy, barium studies and gastric acid output measurements through the gastrostomy. Histological gastritis, low acid output and absence of H. pylori infection were found. Conclusion: We were able to exclude severe gastric disease in our patients.

How often is diagnosis of COPD confirmed with spirometry

BACKGROUND Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality worldwide. Diagnosis is customarily confirmed with spirometry, but there are few studies on documented spirometry use in everyday clinical practice. METHODS In a cross-sectional survey and study of the medical records of primary and secondary care COPD patients aged 18-75 in a Swedish region, patients with COPD were randomly selected from the registers of 56 primary care centres and 14 hospital outpatient clinics. Spirometry data at diagnosis +/-6 months were analyzed. RESULTS From 1114 patients with COPD, 533 with a new diagnosis of COPD during the four-year study period were identified. In 59% (n=316), spirometry data in connection with diagnosis were found in the medical records. Spirometry data with post-bronchodilator forced expiratory volume in 1s (FEV(1))/ vital capacity (VC) ratios were available in 45% (n=241). FEV1/VC ratio <0.70 were found in 160 patients, which corresponds to 30% of the patients with a new diagnosis. Lower age, female gender, current smoking, higher body mass index (BMI) and shorter forced exhalation time were related to COPD diagnosis despite an FEV(1)/VC ratio of >/=0.70. The most common problem in the quality assessment was an insufficient exhalation time. CONCLUSIONS Only a third of Swedish patients with COPD had their diagnosis confirmed with spirometry. Our data indicate that female gender, current smoking, higher BMI and short exhalation time increase the risk of being diagnosed with COPD without fulfilling the spirometric criteria for the disease.

Role of Gastric Acid in Stomal Ulcer after Gastric Bypass

Background: The pathogenetic mechanisms of stomal ulcer after Roux-en-Y gastric bypass (RYGBP) are unclear. In order to study the role of gastric acid, we measured acidity in the proximal pouch using a pH-sensitive probe. Methods: 6 patients (5 females, mean age 45 years old at time of operation) with endoscopically confirmed stomal ulcer, were studied 2 to 6 years after RYGBP. All complained of epigastric pain that improved during proton pump inhibitor (PPI) therapy. Control subjects were 6 females (50 years old) who had had RYGBP at least 5 years earlier and denied symptoms of epigastric pain or heartburn. The pH-sensitive probe (Digitrapper-pH, Medtronic) was passed through the nose to the proximal pouch, guided by the calculated distance and pH response. The probe was left in place for 4 hours. The percentage of time with pH <4 was calculated. Results: The probe could be accurately positioned in the proximal pouch both in symptomatic patients and in controls as evidenced by the acid pH reaction. The proximal pouches of patients with stomal ulcer were significantly more exposed to acid compared to controls. The median percentage of time with pH <4 was 69% and 20% in the stomal ulcer and the control group, respectively (P<0.01). Barium follow-through excluded gastro-gastric fistula in stomal ulcer patients. Conclusion: RYGBP patients with stomal ulcer have increased acid production in their proximal pouch in comparison with asymptomatic RYGBP patients. Gastric acid appears to have an important role in the pathogenesis of stomal ulcer.

Different airway responsiveness profiles in atopic asthma, nonatopic asthma, and Sjögren's syndrome

Background: Different mechanisms may underlie bronchial hyperresponsiveness (BHR) in different diseases. The aim of this study was to investigate the bronchial responsiveness profile produced by three different challenge tests, methacholine, a direct simulus, and two indirect stimuli, adenosine 5′‐monophosphate (AMP) and cold air, in subjects with asthma and patients with Sjögrens syndrome.

Association between low plasma levels of ophthalmic timolol and haemodynamics in glaucoma patients.

ObjectivesThe aims of the study were to assess the correlation between the plasma concentration of ophthalmic timolol and cardiovascular parameters, and the influence of timolol on advanced haemodynamic variables, such as stroke (SI), cardiac (CI) and systemic vascular resistance (SVRI) indices and arterial pulse wave velocity (PWV).MethodsTwenty-five glaucoma or ocular hypertensive patients were treated with 0.5% aqueous and 0.1% hydrogel formulations of timolol using a randomised, double-masked, crossover, multicentre design. All the patients were subjected to passive head-up tilt, electrocardiography, exercise test and measurement of plasma concentration of timolol. In the analysis, the data on the two treatments were combined, and the Spearman correlation coefficients between the plasma level of timolol and physiological effects were calculated.ResultsDuring the head-up tilt test before rising the bed up, the resting heart rate (HR; R=−0.52, P=0.001) and PWV (R=−0.34, P=0.04) were inversely correlated with timolol level. In the upright position, ophthalmic timolol effectively suppressed the rise in HR (R=−0.36, P=0.03). The SI did not change with timolol concentration, while CI diminished as timolol concentration rose (R=−0.39, P=0.02). The SVRI correlated with timolol concentration (R=0.38, P=0.02). In the exercise test, correlation between HR and plasma level of timolol steadily grew stronger as the load increased, reaching R=−0.60 (P<0.0001) at the maximum load. Systolic and diastolic arterial pressures were not associated with the timolol concentration.ConclusionThe plasma concentration of ophthalmic timolol correlates with several haemodynamic effects. As HR decreases, SVRI increases and blood pressure is kept unchanged.

Peak exercise capacity estimated from incremental shuttle walking test in patients with COPD: a methodological study

BackgroundIn patients with COPD, both laboratory exercise tests and field walking tests are used to assess physical performance. In laboratory tests, peak exercise capacity in watts (W peak) and/or peak oxygen uptake (VO2 peak) are assessed, whereas the performance on walking tests usually is expressed as distance walked. The aim of the study was to investigate the relationship between an incremental shuttle walking test (ISWT) and two laboratory cycle tests in order to assess whether W peak could be estimated from an ISWT.MethodsNinety-three patients with moderate or severe COPD performed an ISWT, an incremental cycle test (ICT) to measure W peak and a semi-steady-state cycle test with breath-by-breath gas exchange analysis (CPET) to measure VO2 peak. Routine equations for conversion between cycle tests were used to estimate W peak from measured VO2 peak (CPET). Conversion equation for estimation of W peak from ISWT was found by univariate regression.ResultsThere was a significant correlation between W peak and distance walked on ISWT × body weight (r = 0.88, p < 0.0001). The agreement between W peak measured by ICT and estimated from ISWT was similar to the agreement between measured W peak (ICT) and W peak estimated from measured VO2 peak by CPET.ConclusionPeak exercise capacity measured by an incremental cycle test could be estimated from an ISWT with similar accuracy as when estimated from peak oxygen uptake in patients with COPD.

Comparisons of effects of intravenous and inhaled methacholine on airway physiology in a murine asthma model.

Airway responses to intravenous (i.v.) and inhaled (i.h.) delivery of methacholine (MCh) in BALB/c and C57BL/6 mouse strains have been compared with and without ovalbumin (OVA)-induced airway inflammation. Bronchial reactivity to MCh was assessed in anaesthetised and tracheostomised animals by using an animal ventilator (flexiVent). We partitioned the response of the lungs into airway and parenchymal components in order to compare the contributions of the airways with those of the lung parenchyma to the pulmonary mechanical responses resulting from different routes of MCh administration. Our results indicate disparate physiological responses. Intravenous MCh delivery induced a higher maximum lung resistance than i.h. MCh in OVA-treated BALB/c mice but not in C57BL/6 mice. Inhaled MCh delivery led to a significantly larger fall in lung compliance and a greater impact on peripheral airways than i.v. MCh in both strains. In conclusion, i.v. and i.h. MCh produced disparate effects in different murine strains and variant responses in inflamed airways and healthy controls. The two methods of MCh delivery have important advantages but also certain limitations with regard to measuring airway reactivity in a murine model of allergic asthma.