Does body height reduction influence interpretation of lung function in COPD patients?

Vertebral deformities are prevalent in chronic obstructive pulmonary disease (COPD) patients and may cause excessive loss of height. As height is used for calculating reference values for pulmonary function tests, larger than normal height reduction could cause overestimation of lung function. In this cross-sectional study of 465 COPD patients and 462 controls, we explored how often lung function is misinterpreted due to height reduction in COPD patients, and whether the number or severity of vertebral deformities correlate with height reduction. Measured height was compared to recalled tallest height (RTH) and height calculated from arm span (ASH) to assess height reduction. Vertebral deformities were assessed from radiographs and pulmonary function was assessed using standard formulae. Height reduction was frequent in both the study and control groups, and increased with the number and severity of vertebral deformities. When using current measured height, lung function was overestimated in a significant proportion of COPD patients at relatively modest height reductions. The effects were smallest for forced expiratory volume in 1 s and forced vital capacity, and most pronounced for total lung capacity and residual volume. Therefore, we propose that in COPD patients with excessive height reduction, one might use RTH or ASH in calculating predicted values. Furthermore, such patients should be evaluated for co-existing vertebral deformities and osteoporosis.

High prevalence of vertebral deformities in COPD patients: relationship to disease severity.

Bone mineral density decreases with advancing chronic obstructive pulmonary disease (COPD) severity, but it is not known whether this is reflected in higher fracture rates. The present authors wanted to compare the prevalence of vertebral deformities in COPD patients with those in a population-based reference group to determine whether the number of deformities was related to the severity of COPD and how far the use of oral corticosteroids (OCS) influenced the prevalence of deformities. In the present cross-sectional study of 465 COPD patients and 462 controls, vertebral deformities were found in 31% of the COPD patients and 18% of the controls. In subjects who had never or sporadically used OCS, deformities were found in 29% of the COPD patients and 17% of the controls. In females, the average number of vertebral deformities was almost two-fold when COPD severity increased from Global Initiative of Chronic Obstructive Lung Disease stage II to III. In males, the use of OCS had a small but significant influence. Prevalence of vertebral deformities was significantly higher in chronic obstructive pulmonary disease patients than in the controls. In females, the average number of deformities was related to chronic obstructive pulmonary disease severity even after adjustment for other known risk factors. The difference between patients and controls remained significant even in those who never or sporadically used oral corticosteroids.

Consumption of fruit and berries is inversely associated with carotid atherosclerosis in elderly men.

Epidemiological data suggest that fruit and vegetable consumption is associated with a lowered risk of CVD. We assessed the association between the intima-media thickness (IMT) of the carotid artery and dietary intake of vegetables, fruit and berries in elderly men with a high risk of CVD. Subjects (age 70 +/- 5 years) were survivors from a cohort of 1232 men that participated in the Oslo Diet and Antismoking Study in 1972-3. Measurements of the carotid IMT by high resolution B-mode ultrasound, risk factor assessment and dietary data based on an FFQ were collected in 1997-9. Complete dietary and ultrasound data were available for 547 subjects. The carotid IMT in the highest quartile of dietary intake of fruit and berries was 0.89 (SE 0.18) mm compared with 0.96 (SE 0.25) mm in the lowest quartile, giving a mean difference of 0.075 (SE 0.027) mm (P = 0.033). In multivariate regression analysis increased intake of fruit and berries remained inversely associated with IMT after adjustment for age, cigarette smoking, dietary cholesterol and saturated fat, consumption of milk, cream and ice cream and energy intake (multivariate regression coefficient 0.257; R(2) 0.066; SE 0.209; P < 0.001). The difference of 348 g of fruit and berries per d between the lowest and highest quartile of intake was associated with a 5.5 % adjusted difference in mean IMT. These findings suggest that consumption of fruit and berries may be protective against carotid atherosclerosis in elderly men at high risk of CVD.

Follow-up of diet and cardiovascular risk factors 20 years after cessation of intervention in the Oslo Diet and Antismoking Study.

OBJECTIVE: The Oslo Diet and Antismoking study was a 5-year randomised trial initiated in 1972-1973, which studied the effect of dietary change and smoking cessation for the prevention of coronary heart disease among high-risk middle-aged men. To test the long-term maintenance of lifestyle change, we examined diet and cardiovascular risk factors in subjects initially randomised to the control and intervention groups 20 years after cessation of the intervention. SUBJECTS AND DESIGN: Of the original cohort that included 1232 participants, 910 survivors were identified in 1997 and cardiovascular risk factors were measured in 563 (62%) in 1997-1999. Of these, 558 (99%) also completed questionnaires about their food intake and attitudes to health and diet. RESULTS: Cigarette smoking was nearly halved between baseline and 20-year follow-up in each of the intervention and control groups (P<0.001 within groups), but did not differ between the intervention group (39%) versus the control group (34%); P=0.07. Body mass index increased by 1.4+/-2.6 and 1.6+/-2.6 kg/m(2) between baseline and 20-year follow-up in the intervention and control groups, respectively (P<0.001 within groups; NS between groups). Serum total cholesterol and triglyceride concentrations decreased substantially in subjects treated or untreated with statins (P<0.001 within the intervention and control groups) but did not differ between the groups (total cholesterol change of -1.4+/-1.3 and -1.3+/-1.2 mmol/l, respectively, and triglyceride change of -0.5+/-1.0 mmol/l in both groups). Men in the intervention group reported a less atherogenic fat quality score and lower intakes of fat, saturated fat and cholesterol, higher intakes of long chain polyunsaturated fatty acids, protein and beta-carotene and greater attention to lifestyle and change of diet than the control group (all P<0.05). The fatty acid concentrations did not differ, however, between the intervention and control groups (P>0.05). CONCLUSIONS: No long-term differences in smoking rates or lipid concentrations between the intervention and control groups were observed in the surviving attendees two decades after the end of the trial. Lifestyle intervention still influenced the dietary intake, though modestly.

Lipoatrophic men 44 months after the diagnosis of lipoatrophy are less lipoatrophic but more hypertensive.

OBJECTIVES: To identify clinical factors associated with HIV-associated lipoatrophy and to evaluate body composition changes, blood pressure and lipid levels in lipoatrophic subjects 3-4 years after the atrophy diagnosis. METHODS: Clinical signs of lipoatrophy were assessed in 308 ambulant HIV-positive patients in 2000-2001. Possible clinical risk factors, such as age, gender, race, wasting, duration of HIV infection, presence or absence of AIDS diagnosis, viral load and CD4 count, and detailed information about drug treatment were analysed and explored in a multivariate model. Lipoatrophic white males with triceps skin fold <10 mm were re-examined after 44 months. Signs of lipoatrophy and associated factors, blood pressure, lipid levels, diet and level of exercise at first and second visits were compared. RESULTS: In the multivariate analysis, significant clinical risk factors for lipoatrophy were weight loss >7 kg compared to normal weight [odds ratio (OR) 3.76; 95% confidence interval (CI) 1.80-7.82; P<0.001], current and/or previous use of stavudine (OR 3.72; 95% CI 1.57-8.83; P=0.003) and duration of HIV infection >80 months (OR 2.28; 95% CI 1.13-4.59; P=0.021). Forty of 47 lipoatrophic white males with skin fold < 10 mm were available for re-examination. Of these, 15 (38%) no longer fulfilled the atrophy diagnosis (P<0.001). The prevalence of arm atrophy fell from 63 to 28% (P=0.001) and facial atrophy from 55 to 43% (P=0.23). Use of stavudine for < 36 months was significantly associated with lipoatrophy reversal (OR 5.00; 95% CI 1.15-21.80; P=0.032), but weight gain and increased CD4 count were not. Prevalence of hypertension increased from 28 to 50% (P=0.035), mean systolic blood pressure from 130+/-14 to 136+/-19 mmHg (P=0.021) and diastolic blood pressure from 82+/-10 to 87+/-12 mmHg (P<0.001). In spite of increased use of lipid-lowering drugs (from two to nine patients), levels of total cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides were unchanged. CONCLUSIONS: In this study, we found that weight loss >7 kg, use of stavudine and long duration of HIV infection were significant risk factors for clinical lipoatrophy. Clinical lipoatrophy was partly reversible, and <36 months on stavudine was significantly associated with atrophy reversal. The prevalence of hypertension and the yearly increase of mean blood pressure were disturbingly high in these patients. However, the number of patients in this study was limited, and prospective studies in larger cohorts are required to confirm these findings.

Risk of over-diagnosis of COPD in asymptomatic elderly never-smokers.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has defined stage I chronic obstructive pulmonary disease (COPD) as forced expiratory volume in one second/forced vital capacity (FEV1/FVC)% <70% and a FEV1% predicted of >80%. Stage 2 has been defined as FEV1/FVC <70% and a FEV1% pred of <80%. The authors examined the extent of COPD misdiagnosis using this definition in healthy, never-smoker, asymptomatic adults aged >70 yrs in Bergen, Norway. A respiratory questionnaire was mailed to a random sample of 2,871 persons aged >70 yrs. In a random, well-defined subgroup of 208 never-smoker respondents with no current respiratory disease and significant dyspnoea or heart disease/hypertension complicated with dyspnoea, 71 were able to perform an acceptable spirometry. Approximately 35% of these healthy, elderly never-smokers had an FEV1/FVC% of <70% and would be classified as having at least a stage 1 COPD. This percentage increased with age and in those aged >80 yrs approximately 50% would be classified as having COPD and approximately one-third would have an FEV1 of <80% pred (stage 2 COPD). The estimated 5th percentile of FEV1 was consistently <80% pred. The Global Initiative for Chronic Obstructive Lung Disease criteria will probably lead to a significant degree of over-diagnosis of chronic obstructive pulmonary disease in those aged >70 yrs. The criteria used to define the various stages of chronic obstructive pulmonary disease need to be age-specific.

Plasmapheresis in the treatment of steroid-dependent bronchial asthma.

BACKGROUND: Can plasmapheresis improve disease severity and lung function and reduce steroid doses in severe asthma patients dependent on oral corticosteroids? METHODS: A pilot study with four asthma patients was undertaken using PEF (peak expiratory flow) symptom score, number of puffs of beta2-agonist, and dose of systemic steroids as disease variables. After at least an 8-week run-in, the patients were randomized to a crossover treatment regimen consisting of either 10 days of plasmapheresis or placebo treatment. Each treatment was succeeded by an 8-26-week follow-up period. RESULTS: No patients achieved a significant effect of plasmapheresis treatment according to the established criteria, nor did anyone experience deterioration. CONCLUSIONS: Removing humoral factors extensively over a 10-day period did not significantly influence the clinical condition of the four steroid-dependent asthma patients studied. Circulating humoral factors seem to be of little importance for the maintenance of the established chronic allergic inflammation in these patients. Plasmapheresis does not seem to be a treatment option for this patient category.

[Is it possible to predict nocturnal hypoxemia in snorers?]. / Kan man forutsi nattlig hypoksemi hos snorkere?

We investigated to what extent the initial outpatient clinical findings could predict the results of in-patient nocturnal pulse oximetry in 108 snorers. 30.6% of the patients had oxygen desaturation index (ODI) > or = 5. The lowest SpO2 dip was strongly correlated to ODI (R2 = 0.729). Body mass index (BMI) and FVC were independently correlated to ODI. Relative risk of nocturnal hypoxemia was 3.2 at BMI > 32.0 kg/m2, and 3.0 at FVC < 87% of predicted value, compared with the whole referred group of snorers. Sensitivity of reported apnoea was 0.91, but specificity was only 0.21 with respect to hypoxaemia. Age, sex, hypersomnolence, morning headache, nasal congestion, smoking and consumption of alcohol or sedatives were not predictive of nocturnal hypoxaemia, neither were erythrocyte volume fraction, PaO2, nor PaCO2.

Surgical treatment of spontaneous pneumothorax by wedge resection without pleurodesis or pleurectomy.

OBJECTIVE: Evaluation of wedge resection of the lung without pleurodesis or pleurectomy as a method of surgical treatment for spontaneous pneumothorax in terms of complications, recurrence rate and postoperative complaints. METHODS: Retrospective study of 132 operations for spontaneous pneumothorax in 120 patients (84 men and 36 women: mean age 34 years, range 14-77) performed between 1974 and 1993. The mean observation time was 84 months (range 6-229) and a 100% follow-up rate of all survivors (97%) was achieved. RESULTS: The indications for surgery were recurrent pneumothorax (52%), persisting air leak during first episode (45%), or hemothorax (3%). Perioperative findings were single bullous disease (86%), 2-3 bullae (6%), diffuse bullous disease (5%) and no bullous disease in 3% of the cases. The overall complication rate was 16% (30-day mortality 1%, reoperation for postoperative bleeding 2%, bronchopneumonia 8%, new pneumothorax during hospital stay 5%). The late recurrence rate (operated lung) was 5%. All recurrences were successfully treated by drainage (n = 3), exsufflation (n = 1) or observation only (n = 3). Reoperation was not necessary. Thirty-seven percent of the patients had postoperative complaints which they associated with the operation. CONCLUSION: Lung resection without pleurodesis or pleurectomy is a simple, safe and effective method of the surgical treatment of spontaneous pneumothorax in terms of complications and recurrence rate in patients with limited bullous disease.

[Methotrexate induced pulmonary disease]. / Metotrexatindusert lungesykdom.

Methotrexate may cause pulmonary side effects. Two cases of methotrexate-induced fibrosing alveolitis are reported. One of the patients died from perforated gastric ulcer, the other was successfully treated with systemic steroids. The pulmonary side effects of methotrexate are reviewed. The most common clinical manifestation is fibrosing alveolitis. Pulmonary fibrosis and acute, non-cardiogenic pulmonary oedema are rare.

The influence on the breathing pattern in man of moderate levels of continuous positive and negative airway pressure and of positive end-expiratory pressure during air and CO2 inhalation.

The purpose of this study was to determine in man the effect on the breathing pattern of continuous positive (CPAP), continuous negative (CNAP) and positive end-expiratory (PEEP) airway pressure during air breathing and CO2 inhalation. Six subjects were exposed to CPAP, CNAP and PEEP 0.5 kPa, while five subjects were exposed to CPAP and CNAP 0.8 kPa. End-expiratory lung volume increased during CPAP 0.8 kPa and decreased during CNAP 0.8 kPa. CPAP induced more extensive changes in the ventilatory pattern, and the changes in each parameter were larger than observed during CNAP and PEEP at the same pressure level. In contrast to previous reports we found the effect of CO2 inhalation combined with the effect of pressure breathing to be not stronger than additive. Even moderate CPAP induced alveolar hyperventilation with marked reduction in arterial PCO2 (PaCO2) when breathing air. With increasing fraction of CO2 in the inspiratory gas, the difference in PaCO2 between CPAP and no CPAP disappeared. PEEP also affected the breathing pattern in that it induced an increase in mean inspiratory flow and mean expiratory flow and a reduction in inspiratory duration. Occurrence of ventilatory pauses depended on whether mouthpiece or facemask was used. CPAP and CNAP did not influence the occurrence of pauses, while PEEP prolonged post-expiratory pauses. We conclude that CPAP, CNAP and PEEP induce active ventilatory responses in man and that strong mechanisms are involved during CPAP since PaCO2 is markedly reduced.

Arterial PCO2 and pH in man during 3 days' exposure to 2.8 kPa CO2 in the inspired gas.

It has not been firmly established how respiration adapts to long-term CO2 exposure in man. We have therefore exposed five healthy human subjects to 2.8 kPa CO2 in the inspired gas for about 70 h in a chamber with controlled atmospheric conditions at ambient pressure PCO2 and pH were determined in arterial or arterialized venous blood drawn before, during and after the exposure. One subject was studied twice. We found that PaCO2 increased acutely and then increased further within the 5- to 24-h period of exposure to 2.8 kPa CO2. No consistent change was observed during the following 2 days. At the end of exposure the PaCO2 was 0.5 kPa above the pre-exposure level. When the breathing gas was switched back to room air, PaCO2 promptly returned to pre-exposure values. The secondary rise in PaCO2 within the first day would correspond to a decrease in alveolar ventilation of about 10% assuming constant production and elimination of CO2. Arterial pH remained slightly below the pre-exposure level during the entire exposure period. A slight renal compensation resulting in an increase in base excess of about 1 mmol l-1 may have occurred in the middle part of the exposure period. We conclude that a significant, but moderate, respiratory adaptation takes place during the first day of exposure to an increased inspired load of CO2.

Effects of exercise and CO2 inhalation on the breathing pattern in man.

Conflicting opinions exist concerning the breathing pattern in man during resting and stimulated ventilation. Some but not all investigators have reported the existence of an abrupt change, a 'breakpoint', in the relation between mean tidal volume and mean inspiratory time. Different opinions exist as to whether the slope and the intercept for the relation between mean minute ventilation and mean tidal volume are identical regardless of the mode of stimulating the ventilation. We have studied 10 subjects, at rest and during graded stimulation of ventilation by CO2 inhalation and exercise. No breakpoint was observed in the relations between (1) mean tidal volume and mean inspiratory time and (2) mean tidal volume and mean expiratory time, even if a wide range of tidal volumes was achieved in our subjects. Carbon dioxide inhalation (normoxic or hyperoxic) and exercise gave different regression lines for the relation between mean minute ventilation and mean tidal volume in 8 out of 10 subjects with a larger slope during exercise. At exercise inspiratory time decreased with any increase in tidal volume, while during CO2 breathing no consistent change in inspiratory time was seen. Mean inspiratory flow was linearly related to exercise load and apparently also to arterial carbon dioxide pressure. We conclude that CO2 breathing gives a breathing pattern which is different from that obtained with exercise in the majority of normal subjects. Furthermore, we could not confirm the existence of breakpoints in relations describing the breathing pattern of normal man.

Arterial P CO2 and lung ventilation in man exposed to 1-5% CO2 in the inspired gas.

Conflicting results have been published on the shape of the curve relating the change in lung ventilation to the change in alveolar or arterial PCO2 induced by increased inspired CO2 (the CO2 sensitivity). In this study eight human subjects with in-dwelling arterial cannulae were each exposed to five different levels of increased inspired CO2 (1-5%). Arterial PCO2 and ventilation were measured in the 7th minute of each period of CO2 exposure. Each CO2 exposure period was flanked by control periods in which similar measurements were carried out during air breathing. We found non-linear increases in both ventilation and arterial PCO2 with increasing levels of inspired CO2. When 5% CO2 in air was inspired the arterial PCO2 increased by about 15% of the inspired CO2 load. There was no significant non-linearity in the relation between change in alveolar ventilation (normalized to body surface) and change in arterial PCO2. The inter-individual variation in CO2 sensitivity was less when alveolar ventilation was normalized to the CO2 output rather than to body surface area. We conclude that the sensitivity to CO2 is close to constant within the range 0-5% CO2 in the inspired gas.

CO2 sensitivity in humans breathing 1 or 2% CO2 in air.

Ventilation increases when the concentration of CO2 in the inspired gas is increased, thereby limiting the increase in alveolar and arterial PCO2. The extent of this compensation at low levels of inspired CO2 has been debated. In five healthy humans, we have measured arterial PCO2, arterial pH and ventilation during exposure to 1 and 2% CO2 in the inspired gas. Each exposure lasted at least 7 min and arterial blood was sampled over at least 30 s during the last minute of each period. The ventilation was measured in the sixth and seventh min. The protocol included the sequences: control-test-control and test-control-test with 'test' representing CO2 loading and 'control' 0% CO2, respectively. We found that arterial PCO2 increased and pH decreased at both levels of inspired CO2. The mean increase in arterial PCO2 was 0.09 and 0.25 kPa, at CO2 1 and 2%, respectively. Three subjects were exposed to 1% CO2 in the inspired gas for 28 min flanked by similar control periods. In each period arterial blood samples were taken at 2- or 3-min intervals. Arterial PCO2 remained elevated for at least 20 min during the CO2 loading. The sensitivity to CO2 (ratio of increase in ventilation to increase in arterial PCO2) was within the range described by others at higher levels of inspired CO2. Arterial PCO2 increased by about 10% of the imposed load. We conclude that the increase in ventilation provides only incomplete compensation for exposure to CO2: arterial CO2 is increased and arterial pH decreased also at very low levels of inspired CO2.

Changes in human cerebral blood flow due to step changes in PAO2 and PACO2.

The effect of moderate hypoxia on cerebral blood flow (CBF) in man has not been well described, and little is known about the interaction of changes in arterial PO2 and PCO2 as regards CBF. Using a non-invasive doppler ultrasound method we have measured the instantaneous mean blood velocity (which is proportional to CBF as long as the cross-section of the vessel is constant) in the carotid artery in four healthy unanaesthetized subjects. We found in all subjects that a reduction in alveolar PO2 from about 13 to about 8.7 kPa with maintained constant alveolar PCO2 (PA, CO2) caused CBF to increase gradually over 10 min (half-time about 4 min) to about 125% of control. The CBF decreased quickly (half-time about 45 s) towards control when alveolar PO2 was reset to 13 kPa. As measured 5 min after a step-change in PA, O2, the change in CBF was independent of PA, CO2 within the range 3.3-6.7 kPa. An increase in PA, O2 to about 33 kPa reduced CBF only if PA, CO2 was in the hypercapnic range. Unexpectedly we found that the CBF response showed 'adaptation' during both maintained increase and decrease in PA, CO2. The CBF started to return towards control level within 10 min after induction of hypo- or hypercapnia. We conclude that also moderate hypoxia causes increased CBF in unanaesthetized man within a wide range of PA, CO2.