Reduced lung function predicts increased fatality in future cardiac events. A population-based study

Objective. Moderately reduced lung function in apparently healthy subjects has been associated with incidence of coronary events. However, whether lung function is related to the fatality of the future events is unknown. This study explored whether reduced forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV₁) in initially healthy men is related to the fatality of the future coronary events. Design. Prospective cohort study. Setting. Population‐based study from Malmö, Sweden. Subjects. A total of 5452 healthy men, 28–61 years of age. Main outcome measures. Incidence of first coronary events was monitored over a mean follow‐up of 19 years. The fatality of the future events was studied in relation to FEV and FVC. Results. A total of 589 men suffered a coronary event during follow‐up, 165 of them were fatal during the first day. After risk factors adjustment, low FEV or FVC were associated with incidence of coronary events (fatal or nonfatal) and this relationship was most pronounced for the fatal events. Amongst men who subsequently had a coronary event, the case‐fatality rates were higher in men with low FEV or FVC. Adjusted for risk factors, the odds ratio for death during the first day was 1.00 (reference), 1.63 (95% CI: 0.9–3.1), 1.86 (1.0–3.5) and 2.06 (1.1–3.9), respectively, for men with FVC in the 4th, 3rd, 2nd, and lowest quartiles (trend: P < 0.05). FEV showed similar relationships with the fatality rates. Conclusion. Apparently healthy men with moderately reduced lung function have higher fatality in future coronary events, with a higher proportion of coronary heart disease deaths and less nonfatal myocardial infarction.     

Comparison of FEV(3), FEV(6), FEV(1)/FEV(3) and FEV(1)/FEV(6) with usual spirometric indices

Background and objective: Pulmonary function tests play an important role in the management of pulmonary diseases. One of the tests that are widely used is spirometry. Performing an acceptable spirometry manoeuvre according to the standards set by the American Thoracic Society/European Respiratory Society is difficult. The aim of this study was to compare forced expiratory volume in 3 s (FEV₃) and forced expiratory volume in 6 s (FEV₆) with forced vital capacity (FVC), and forced expiratory volume in 1 s FEV₁/FEV₃ and FEV₁/FEV₆ with FEV₁/FVC, in order to substitute the usual spirometric manoeuvres with manoeuvres that are easier to perform. Methods: In a cross‐sectional study, spirometry was performed for 588 subjects who were referred for occupational health evaluations. The accuracy of FEV₃, FEV₆, FEV₁/FEV₃ and FEV₁/FEV₆ was compared with that of FVC and FEV₁/FVC. Chi‐square tests and kappa tests were used to analyse the data. Results: Individuals with normal (n = 297) and abnormal spirometry (n = 291) were evaluated. The sensitivity, specificity, positive predictive value and negative predictive value of FEV₁/FEV₆, as compared with that of FEV₁/FVC for detecting obstruction, were 93.56, 99.32, 98.95 and 96.09, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of FEV₆, as compared with that of FVC for detecting restriction, were 96.68, 98.65, 96.68 and 98.65, respectively. Conclusions: FEV₆ and FEV₁/FEV₆ can be used as surrogates for FVC and FEV₁/FVC, respectively, and these parameters showed acceptable sensitivity, specificity, positive predictive value and negative predictive value for occupational health evaluations.     

IgG subclass antibody responses to alginate from Pseudomonas aeruginosa in patients with cystic fibrosis and chronic P. aeruginosa infection.

Chronic bronchopulmonary infection with alginate-producing, mucoid Pseudomonas aeruginosa is characteristically associated with cystic fibrosis (CF). A significant correlation between the antibody response to alginate and poor lung function has been reported. Enzyme-linked immunosorbent assays were developed for the quantitation of human IgG1, IgG2, IgG3, and IgG4 antibodies to P. aeruginosa alginate. We investigated the pattern of IgG subclass antibodies against P. aeruginosa alginate in serum of patients with CF, others with chronic P. aeruginosa infection, and healthy controls. Healthy controls and patients with CF, before they acquired P. aeruginosa infection, had no or very low titers of antibodies against P. aeruginosa alginate. The latter with chronic infection had significantly higher antibody levels than all others groups, including patients with chronic P. aeruginosa infection but no CF. CF with chronic P. aeruginosa infection led to an inverse correlation between lung function parameters and levels of IgG3 and IgG4. Fifty-seven patients with CF have been followed for an average of 12 years with multiple antibody assays covering the preinfection, early, and late stage of chronic infection. All of them developed IgG1 and IgG3 antibodies to alginate at the start of infection. IgG2 antibodies developed later and showed only a slow increase during the chronic infection. Patients who died had significantly higher IgG2 anti-alginate antibody levels than other investigated groups. Elevated levels of IgG2 and IgG3 antibodies to P. aeruginosa alginate are a sign of poor prognosis in CF.     

Effects of Repeated Deep Inspirations on Recovery from Methacholine-Induced Airway Narrowing in Normal Subjects

Background. A single deep inspiration (DI) is known to be a potent bronchodilator but it is not known if repeated DI can accelerate sustained recovery from bronchoconstriction. Methods. We induced sustained bronchoconstriction using increasing concentrations of nebulized methacholine (Mch) during tidal breathing and assessed airway narrowing by measuring respiratory resistance (Rrs) using forced oscillation in six healthy subjects. On separate days we examined the effects of DI every 3 minutes and of prohibition of DI on recovery of Rrs for 30 minutes after the end of Mch nebulization. Results. Bronchoconstriction (Rrs ～ 150% above baseline) was induced. DI during recovery had a transient bronchodilator effect but no cumulative effect. At 30 minutes after end of nebulization (and 2 minutes after the last DI) Rrs was 87% above baseline compared to 93% above baseline when DI was prohibited. Conclusion. Recovery from induced bronchoconstriction with methacholine was slow (～ 2%/min) and not accelerated by frequent DI.     

Effects of Repeated Deep Inspirations on Recovery from Methacholine-Induced Airway Narrowing in Normal Subjects

Background. A single deep inspiration (DI) is known to be a potent bronchodilator but it is not known if repeated DI can accelerate sustained recovery from bronchoconstriction. Methods. We induced sustained bronchoconstriction using increasing concentrations of nebulized methacholine (Mch) during tidal breathing and assessed airway narrowing by measuring respiratory resistance (Rrs) using forced oscillation in six healthy subjects. On separate days we examined the effects of DI every 3 minutes and of prohibition of DI on recovery of Rrs for 30 minutes after the end of Mch nebulization. Results. Bronchoconstriction (Rrs ∼ 150% above baseline) was induced. DI during recovery had a transient bronchodilator effect but no cumulative effect. At 30 minutes after end of nebulization (and 2 minutes after the last DI) Rrs was 87% above baseline compared to 93% above baseline when DI was prohibited. Conclusion. Recovery from induced bronchoconstriction with methacholine was slow (∼ 2%/min) and not accelerated by frequent DI.     

Baseline and post-bronchodilator interrupter resistance and spirometry in asthmatic children

In children unable to perform reliable spirometry, the interrupter resistance (R_int) technique for assessing respiratory resistance is easy to perform. However, few data are available on the possibility to use R_int as a surrogate for spirometry. We aimed at comparing R_int and spirometry at baseline and after bronchodilator administration in a large population of asthmatic children. We collected retrospectively R_int and spirometry results measured in 695 children [median age 7.8 (range 4.8–13.9) years] referred to our lab for routine assessment of asthma disease. Correlations between R_int and spirometry were studied using data expressed as z‐scores. Receiver operator characteristic curves for the baseline R_int value (z‐score) and the bronchodilator effect (percentage predicted value and z‐score) were generated to assess diagnostic performance. At baseline, the relationship between raw values of R_int and FEV₁ was not linear. Despite a highly significant inverse correlation between R_int and all of the spirometry indices (FEV₁, FVC, FEV₁/FVC, FEF_25–75%; P < 0.0001), R_int could detect baseline obstruction (FEV₁ z‐score ≤ ?2) with only 42% sensitivity and 95% specificity. Post‐bronchodilator changes in R_int and FEV₁ were inversely correlated (rhô = ?0.50, P < 0.0001), and R_int (≥35% predicted value decrease) detected FEV₁ reversibility (>12% baseline increase) with 70% sensitivity and 69% specificity (AUC = 0.79). R_int measurements fitted a one‐compartment model that explained the relationship between flows and airway resistance. We found that R_int had poor sensitivity to detect baseline obstruction, but fairly good sensitivity and specificity to detect reversibility. However, in order to implement asthma guidelines for children unable to produce reliable spirometry, bronchodilator response measured by R_int should be systematically studied and further assessed in conjunction with clinical outcomes. Pediatr Pulmonol. 2012. 47:987–993. © 2012 Wiley Periodicals, Inc.     

Effects of administration of aerosolized recombinant human deoxyribonuclease on resting energy expenditure in patients with cystic fibrosis

By improving pulmonary function in patients with cystic fibrosis (CF), recombinant human deoxyribonuclease (rhDNase) may affect resting energy expenditure (REE). To examine this hypothesis, we measured REE by indirect calorimetry in seven patients with CF before (day 0) and 2 weeks after (day 15) administration of aerosolized rhDNase. Baseline REE was higher in all patients than predicted for age, sex, and weight (mean ± SEM 128±4.9%; range, 116–147%). After 2 weeks of aerosolized rhDNase, mean forced vital capacity (FVC) (in % of predicted values) improved significantly from 54.1 ± 2.2 to 66.3±4.2% (mean improvement, 12.3%; 95% Cl, 2.8,21; P < 0.05) and REE decreased by 11.0% (95% Cl 3.2, 17.5; P < 0.05). In addition, the larger the improvement in FVC in response to rhDNase the greater the decrease in energy expenditure (r – 0.88). The REE decreased in all patients who had an increase in FVC and remained unchanged in two patients who had no change in FVC. We conclude that patients with CF whose lung function improve in response to aerosolized rhDNase have an acute and proportionate reduction in their resting energy expenditure. Pediatr Pulmonol. 1994;18:150–154. © 1994 Wiley-Liss, Inc.     

Ethnic differences in spirometry measurements in China: Results from a large community‐based epidemiological study

Background and objective

No previous studies have examined differences in spirometry measurements among ethnic populations in China, and factors which may influence ethnic differences are unclear. Our study aimed to investigate whether forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) differ among Han Chinese and other ethnic minorities in China.

Methods

We recruited 7137 individuals aged 35–70 years from four areas of China inhabited by ethnic minority groups between 2007 and 2009. We conducted spirometry tests for all available participants, and compared FEV₁ and FVC among Uygur, Hui, Mongolian, Dai and Han Chinese ethnicities, using nonlinear multiplicative regression models.

Results

A total of 2005 healthy never‐smokers were enrolled in the analysis. For all ethnicities, spirometry values increased with height and decreased with age; FEV₁ and FVC were consistently higher in males than in females. Compared with Han Chinese, FEV₁ was 4.42% (95% CI: 2.11–6.78%) higher in Mongolians, 4.08% (95% CI: 1.33–6.76%) lower in Uygurs, 4.39% (95% CI: 1.33–7.35%) lower in Hui people and 4.72% (95% CI: 1.80–7.55%) lower in Dai people, after adjusted for potential confounders including height, age, sex and place of residence. We observed similar differences for FVC.

Conclusions

We detected significant differences in spirometry measurements among ethnic populations in China. Such differences cannot be fully explained by demographic, anthropometric or socioeconomic factors, but may also be attributed to genetic background as well as indoor and outdoor environmental exposures that need further investigation.

     

Identification and comparison of insulin pharmacokinetics injected with a new 4‐mm needle vs 6‐ and 8‐mm needles accounting for endogenous insulin and C‐peptide secretion kinetics in non‐diabetic adult males

Aims/Introduction

Many patients with diabetes now use 5‐, 6‐ or 8‐mm needles for insulin injection. However, it is unclear whether needle length, particularly for shorter needles, affects the pharmacokinetic properties of insulin.

Materials and Methods

This was a three‐way, randomized, cross‐over, single‐center study involving 12 healthy Japanese adult males (age 27.4 ± 4.14 years; weight 64.2 ± 5.2 kg; body fat percentage 18.2 ± 1.5%). Participants received a subcutaneous (abdomen) dose of insulin lispro (1.5 U for participants weighing 55 to <65.0 kg; 2.0 U for participants weighing 65.0 to <80.0 kg) delivered using a 32‐G × 4 mm (32G × 4), 31‐G × 8 mm (31G × 8) or 32‐G × 6 mm (32G × 6) needle with a 3–7‐day washout between doses. Pharmacokinetic parameters of exogenous insulin were identified using non‐linear least squares, where the total insulin concentration was fit to the measured plasma insulin concentration using an overall combined model that accounted for C‐peptide/insulin secretion in addition to the injected dose.

Results

Maximum concentration and area under the curve for 0 to infinity min for insulin were bioequivalent for the 32G × 4 needle relative to the 32G × 6 and the 31G × 8 needles. The time to the maximum insulin concentration was bioequivalent for the 32G × 4 needle relative to the 32G × 6 needle, but not the 31G × 8 needle.

Conclusions

The use of 4‐mm needles is unlikely to change the pharmacokinetic properties of insulin when injected subcutaneously in adults. This trial was registered with UMIN‐CTR (no. UMIN000004469).     

Type 2 diabetes in young adults in Central Auckland: demography and complications

Background

Type 2 diabetes (T2D) in young adults is associated with a high risk of diabetes complications.

Aims

To investigated the demography and the emergence of complications of young adults with T2D in the central Auckland region where there has been substantial immigration.

Methods

In total, 310 young adults with T2D (<40 years) were registered with the Auckland Diabetes Centre in 2015. We documented demographic, anthropometric and metabolic variables and prevalence and the emergence of complications.

Results

Three demographic groups accounted for 243 participants (78%): 135 (44%) were migrants of Asian or Pacific Island origin, diagnosed a median 9 years after migration at a mean age of 28 ± 6 years; 88 (29%) were New Zealand‐born Pāsifika descent, with a high prevalence of morbid obesity and 37 (12%) had major mental illness or intellectual disability. At diagnosis, the median HbA1c was 80 mmol/mol, and in 28%, it was ≥100 mmol/mol. A median 6 years after diagnosis, 56% had some degree of retinopathy, with the prevalence related both to the duration of diabetes and glycaemic control (P = 0.001). Forty‐four percent of subjects had abnormal albuminuria at diagnosis (12% with macroalbuminuria). Increased albuminuria was strongly associated with obesity (P = 0.002). The development of CKD stages 4–5 was related both to the severity of retinopathy and degree of albuminuria at diagnosis (P = 0.0001). Major cardiovascular events were related to the severity of retinopathy at diagnosis (P = 0.0001).

Conclusions

New migrants, New Zealand‐born Pāsifika and patients with mental illness or an intellectual disability comprise the bulk of young onset T2D. The disease is aggressive, and by the age of 40, patients are already developing advanced complications.     

Measurements of immature platelets with haematology analysers are of limited value to separate immune thrombocytopenia from bone marrow failure

Detection of immature platelets in the circulation may help to dissect thrombocytopenia due to platelet destruction from bone marrow failure (BMF ). We prospectively tested the predictive value of immature platelets, measured as immature platelet fraction (IPF ) on the XE‐5000 (Sysmex, Kobe, Japan) or percentage of reticulated platelets (rPT ) on the CD Sapphire (Abbott Diagnostics, Santa Clara, CA, USA) to separate immune thrombocytopenia (ITP ) from BMF (leukaemia, myelodysplastic syndrome, aplastic anaemia). We analysed 58 samples of patients with BMF , 47 samples of patients with ITP and 97 controls. Median rPT (CD Sapphire) was increased to 9·0% in ITP and to 10·9% in BMF , compared to 1·9% in controls. Median IPF (XE‐5000) was 16·2% in ITP , 10·2% in BMF and 2·5% in controls. We found an inverse correlation between high fractions of immature platelets and low platelet counts in thrombocytopenic samples regardless of the diagnosis. In conclusion, we observed a broad overlap of immature platelets between ITP and BMF , which may be caused by an accelerated release of immature platelets in any thrombocytopenic state and decreased production in many patients with ITP . Despite this, IPF (XE‐5000) had some power to discriminate ITP from BMF , whereas rPT (CD Sapphire) was of no predictive value.