The FEV1/FEV6 ratio is a good substitute for the FEV1/FVC ratio in the elderly.

AIMS: To determine the agreement between the FEV1/FEV6 ratio and the FEV1/FVC ratio in an elderly population. METHOD: The study sample consisted of 3874 participants in a cross-sectional population survey in Troms?, Norway, aged 60 years or more, in whom acceptable spirometry had been obtained. Mean differences between the FEV1/FEV6 ratio (%) and the FEV1/FVC ratio (%) were calculated according to age, sex, smoking habit, and the degree of airflow limitation. ROC-curve analysis and Kappa-statistics were used to estimate the utility of the FEV1/FEV6 ratio in predicting an FEV1/FVC ratio < 70%. RESULTS: The mean difference between FEV1/FEV6% and FEV1/FVC% was 2.7% in both men and women. The difference between the two measures increased somewhat with increasing age, and was more pronounced with smoking and decreasing FEV1/FVC ratio. The value for the FEV1/FEV6 ratio which best predicted an FEV1/FVC ratio of 70%, was 73%, and a very good agreement was found between these two cut-off values (kappa = 0.86). CONCLUSION: The FEV1/FEV6 ratio appears to be a good substitute for the FEV1/FVC ratio in an elderly population.     

FEV1/FEV6 is effective as a surrogate for FEV1/FVC in the diagnosis of chronic obstructive pulmonary disease

Background and objectiveChronic Obstructive Pulmonary Disease (COPD) causes substantial morbidity and mortality across the globe. Diagnosis of COPD requires post-bronchodilator FEV1/FVC <0.70 as per GOLD Guidelines. FVC maneuver requires a minimum of 6 seconds of forceful expiration with no flow for 1 second for an accepted effort, which lacks any fixed cut-off point. This leads to discomfort, especially in advanced COPD and old aged population. We conducted this study to find the utility of FEV1/FEV6 as a surrogate for FEV1/FVC, the correlation between the two ratios, and the fixed cut-off value of FEV1/FEV6 for COPD diagnosis.MethodsThis was a prospective, cross-sectional study approved by the institutional ethics committee conducted from January 2017 to November 2018. Consented patients above 18 years suspected of COPD underwent Spirometry as per ATS guidelines. FEV1, FEV6, FEV1/FEV6 and FEV1/FVC ratios were recorded from the best acceptable maneuver.ResultsOut of 560 screened patients, 122 diagnosed as COPD. The correlation coefficient between the post-bronchodilator FEV1/FVC ratio and FEV1/FEV6 ratio was 0.972 (p < 0.01). The relationship between the post-bronchodilator FEV1/FVC ratio and FEV1/FEV6 ratio (linear regression analysis) was found out as: FEV1/FVC = ?1.845 + 1.009(FEV1/FEV6). Using this formula, the post-bronchodilator FEV1/FEV6 value of 71.845 was obtained corresponding to the post-bronchodilator FEV1/FVC value of 70.00.ConclusionWe found a positive correlation coefficient (r = 0.972, p < 0.001) between the FEV1/FEV6 and FEV1/FVC ratios and the cut off value of 71.845 (p < 0.01) for the post-bronchodilator FEV1/FEV6 ratio for the diagnosis of COPD. Thus FEV1/FEV6 should be used as a surrogate for FEV1/FVC for the diagnosis of COPD.     

Effect of Bilateral Lung Volume Reduction Surgery on FEV1 Decline in Severe Emphysema

Study Objective. To examine whether lung volume reduction surgery (LVRS) alters the anticipated natural rates of decline in FEV₁. Design. Retrospective analysis of spirometry results (188 studies) in patients before and after bilateral LVRS. Setting. Large, urban, academic medical center. Patients. 25 patients with severe emphysema (mean (SD) age 60 ± 8 yrs; FEV₁ 0.74 ± 0.29 L, 29% predicted). Interventions. Bilateral LVRS performed via median sternotomy, with areas targeted for resection based on preoperative evaluation using high-resolution computed tomography, quantitative perfusion scans, and intraoperative inspection of the lungs. Linear regression analysis was performed on each patient using all serial postbronchodilator FEV₁ values from before and after LVRS. Results. Lung function data were available between 2–1001 days prior to LVRS and 71–1169 days after LVRS. Comparison of single pre- and post-LVRS FEV₁ results confirmed a significant post-operative (3 month) improvement in lung function. The calculated rate of decline in FEV₁ prior to LVRS was 202 ± 205 mL/yr. Following LVRS, the rate of decline in FEV₁ was unchanged at 178 ± 150 mL/yr (p = 0.64). Conclusions. In patients with severe emphysema, bilateral LVRS does not appear to significantly alter the rate of FEV₁ decline.     

Individual FEV1 Trajectories Can Be Identified from a COPD Cohort

Objective: We aim to make use of clinical spirometry data in order to identify individual COPD-patients with divergent trajectories of lung function over time. Study Design and Setting: Hospital-based COPD cohort (N = 607) was followed on average 4.6 years. Each patient had a mean of 8.4 spirometries available. We used a Hierarchical Bayesian Model (HBM) to identify the individuals presenting constant trends in lung function. Results: At a probability level of 95%, one third of the patients (180/607) presented rapidly declining FEV₁ (mean -78 ml/year, 95% CI -73 to -83 ml) compared to that in the rest of the patients (mean -26 ml/year, 95% CI -23 to -29 ml, p ≤ 2.2 × 10^-16). Constant improvement of FEV₁ was very rare. The rapid decliners more frequently suffered from exacerbations measured by various outcome markers. Conclusion: Clinical data of unique patients can be utilized to identify diverging trajectories of FEV₁ with a high probability. Frequent exacerbations were more prevalent in FEV₁-decliners than in the rest of the patients. The result confirmed previously reported association between FEV₁ decline and exacerbation rate and further suggested that in clinical practice HBM could improve the identification of high-risk individuals at early stages of the disease.     

FEV1%与FEV1/FVC作为COPD气流阻塞判定指标的比较研究

目的　对FEV1%与FEV1/FVC作为COPD气流阻塞判断标准进行比较分析。方法　对 15 8例慢性支气管炎和肺气肿患者 ,34例限制性通气功能障碍疾病的患者及 34例正常人的肺功能进行前瞻性的分析研究。结果　作为COPD气流阻塞判断指标 ,FEV1%与FEV1/FVC呈高度直线正相关 (P <0 0 1) ,FEV1/FVC敏感性高 ,漏诊率低。作为分级标准 ,两者的百分比并不一致 ,FEV1/FVC受FEV1与FVC下降的不一致影响 ,与FEV1%比较 ,中度略有上升 ,重度则明显增高。结论　在确定有无气流阻塞诊断COPD时 ,FEV1/FVC较好 ,在气流阻塞程度分级时 ,FEV1%较好     

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.     

Minimal Clinically Important Differences in COPD Lung Function

The FEV₁ is widely used by physicians in the diagnosis, staging, treatment, monitoring and establishing prognosis for patients with COPD. The MCID is the smallest difference which patients perceive as beneficial and which would mandate a change in patient management. A precise MCID for FEV₁ has not been established.

In attempt to establish a MCID for predose or trough FEV₁, several limitations need to be addressed. There are issues such as reproducibility, repeatability, acceptability, variability, placebo effect, and equipment effects. Patient factors, such as baseline level of FEV₁, albuterol reversibility, diurnal variation, influence the results.

Nonetheless, using anchoring techniques, a change in pre dose FEV₁ of about 100 mL can be perceived by patients, correlates with fewer relapses following exacerbations and is in the range usually achieved with bronchodilators approved for COPD.

In the future, consistent reporting of spirometric variables, such as a predose FEV₁ and other outcomes, can be incorporated into a more quantitative effort to establish the MCID. Also distributional/statistical methods may be useful in determining the MCID FEV₁.     

第一秒与六秒用力呼气容积比值检测气流阻塞的临床研究

目的 探讨在肺功能测定中能否用第1秒用力呼气量与6秒用力呼气量比值（FEV1/FEV6）代替第1秒用力呼气量与肺活量比值（FEV1/FVc）的可行性.方法 对256名慢性阻塞性肺病（COPD）患者和174名非COPD患者进行肺功能检测,收集FVC、FEV6、FEV1/FVC、FEV1/FEV6等数据.比较FEV6与FVC以及FEV1/FEV6与FEV1/FVC的相关性;并以FEV1/FVC〈70%作为判断气流阻塞的标准,计算相应FEV1/FEV6检测气流阻塞的敏感性和特异性.结果 （1）FEV6与FVC以及FEV1/FEV6与FEV1/FVC均呈强正相关关系;（2）根据ROC曲线结果,取FEV1/FEV6为〈72.6%,其诊断气流阻塞的敏感性和特异性分别达到97.7%和98.4%.结论 FEV1/FEV6能够代替FEV1/FVC检测气流阻塞。     

A literature review of the evidence that a 12% improvement in FEV1 is an appropriate cut-off for children

Introduction: A well-performed spirometry, using a change in forced expiratory volume in one second (FEV₁) after albuterol, is commonly used to support the likelihood of an asthma diagnosis. The current standard, accepted by the 2007 National Heart Lung and Blood Institute Asthma Expert Panel Report-3 (EPR-3) guidelines, is a 12% improvement in the FEV₁ after a bronchodilator. Objective: We sought to determine whether existing studies support or refute using a 12% improvement as a significant change in FEV₁ in children and adolescents. Data sources: We reviewed the literature of children and adolescents using Medline searches to discover pertinent population studies and comparative studies that included FEV₁ measurements. Result: The majority of the discovered studies suggest a less stringent improvement in FEV₁ in children might be applicable. Conclusion: Supported by the published literature, we suggest an alternative interpretive strategy of expressing the results of a spirometry measurement when a diagnosis of asthma in a child is being considered using a bronchodilator response.     

Association of Dopamine-related Gene Alleles,Smoking Behavior and Decline in FEV1 in Subjects with COPD: Findings from the Lung Health Study

Abstract

Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). Specific dopamine related gene alleles have previously been found to be associated with smoking initiation, maintenance and cessation. We investigated the association between specific dopamine related gene alleles and both change in smoking behavior and lung function change over time in individuals with mild-to-moderate COPD. Subjects included a subset of participants in the Lung Health Study (LHS), a smoking intervention study in smokers with mild to moderate COPD. Smoking status was determined and lung function performed at baseline and annually for 5 years. In post-hoc analyses, we assessed the association of the dopamine receptor (DRD2) TaqI A1⁺ allele (A1A1, A1A2 genotypes) and A1^? allele (A2A2 genotype), and the dopamine transporter (DAT) 9R⁺ allele (9R9R and 9R10R genotypes) and 9R^? allele (10R10R genotype) with both changes in smoking status and lung function in a subset of LHS subjects. No significant associations were noted between variants in these genes and success in smoking cessation. However, in exploratory analyses that did not adjust for multiple comparisons, sustained male (but not female) quitters with the DRD2 A1^? allele and/or the DAT 9R⁺ allele showed an accelerated decline in FEV₁ similar to that of continuing smokers over 5 years after quitting smoking. These preliminary findings suggest that dopamine-related genes may play a role in the progression of COPD, at least in the subset of male ex-smokers whose disease continues to progress despite sustained quitting, and warrants additional confirmatory and mechanistic studies.     

Preparation and Electrochemical Properties of LiNi2/3Co1/6Mn1/6O2 Cathode Material for Lithium-Ion Batteries

The cathode material LiNi_2/3Co_1/6Mn_1/6O₂ with excellent electrochemical performance was prepared successfully by a rheological phase method. The materials obtained were characterized by X-ray diffraction, scanning electron microscopy, electrochemical impedance spectroscopy and charge-discharge tests. The results showed that both calcination temperatures and atmosphere are very important factors affecting the structure and electrochemical performance of LiNi_2/3Co_1/6Mn_1/6O₂ material. The sample calcinated at 800 °C under O₂ atmosphere displayed well-crystallized particle morphology, a highly ordered layered structure with low defects, and excellent electrochemical performance. In the voltage range of 2.8–4.3 V, it delivered capacity of 188.9 mAh g⁻¹ at 0.2 C and 130.4 mAh g⁻¹ at 5 C, respectively. The capacity retention also reached 93.9% after 50 cycles at 0.5 C. All the results suggest that LiNi_2/3Co_1/6Mn_1/6O₂ is a promising cathode material for lithium-ion batteries.     

慢阻肺中第一秒与六秒用力呼气容积比值应用研究

目的探讨第1秒用力呼气容积与6秒用力呼气容积比值（FEV1／FEV6）在慢性阻塞性肺疾病（COPD）诊断方面的临床价值。方法对120例COPD稳定期患者和80例健康者进行肺量测定,前者依据中华医学会制定的《慢性阻塞性肺疾病诊治指南（2007年修订版）》进行分级,分为COPDI-Ⅱ级组、Ⅲ-Ⅳ级组。结果COPDI-Ⅱ级组FEV1／pre、FEV1／FVC、FEV1／FEV6较对照组明显降低,而COPI）Ⅲ-Ⅳ级组与对照组相比,FVC／pre、FEV6／pre、FEV1／pre、FEV1／FVC、FEV1／FEV1显著降低。COPDI-Ⅱ级组FEV1／pre、FVC／pre下降幅度比FEV1／FVC、FEV1／FEV6低;在COPDⅢ-Ⅳ级组FEV,／pre、FVC／pre的下降幅度比FEV。／FVC、FEV,／FEV。的下降幅度要高。COPDⅢ-Ⅳ级组的CV[FVC]高于COPDI-Ⅱ级组和对照组。FEV1／FEV6和FEV1／FVC呈显著正相关。结论相比FVC,FEV6有着更好的重复性,而FEV1／FEV6和FEV1／FVC也有着显著的相关性,同样可以准确反映气流受限,且测试更为简单。     

Blood gases at rest and during exercise in patients with alpha1-Pi deficiency

Alpha1-protease inhibitor (Pi) deficiency is associated with a protease-anti-protease imbalance leading to premature destruction of lung tissue and early emphysema. Little is known about the blood gases of these patients in the various stages of the disease. The purpose of this study was to evaluate blood gases in patients with alpha1-Pi deficiency when patients were at rest and during exercise, and to correlate these with lung function measurements. A total of 369 patients with severe alpha1-Pi deficiency had pulmonary function test and blood gas analysis, 282 also had blood gases taken during steady state submaximal exercise testing. Only 21% of the patients had normal blood gases at rest; 71% had mild hypoxaemia; 8% had severe hypoxaemia. Surprisingly, 61% of the patients with mild lung disease and a FEV1 of more than 65% predicted were hypoxaemic. During exercise 65% of the patients had a drop in PO2 of more than 0.40 kPa. FEV1 was a significant predictor for the PO2 values at rest and during exercise. During exercise the arterial-alveolar gradient increased in about 50% and decreased in 25% of the patients. Many patients with alpha1-Pi have blood gas abnormalities. Impaired blood gases in early stages of the disease result in a discrepancy between lung function parameters and blood gases. FEV1 measurements inadequately capture the extent of lung disease in patients with alpha1-Pi deficiency, and both blood gases at rest and during exercise are needed in the assessment of all stages of the disease.     

Bronchodilatation Effects of a Small Volume Spacer Used with a Metered-Dose Inhaler

Background and objective. In an effort to improve the delivery of drugs to the lungs, various spacer devices have been developed to attach to metered-dose inhalers (MDIs). The aim of the study was to determine whether use of a small volume tube spacer with MDI is associated with better bronchodilatation. Methods. We assessed bronchodilatation by measuring forced expiratory volume in 1 second (FEV₁) before and after inhalation of fenoterol 0.4 mg (2 puffs) delivered by using a MDI in four different ways: with or without a spacer alone or with a mouth rinse of 100 mL of water immediately after inhalation with or without a spacer. Results. A total of 303 patients who had a positive bronchodilator test were studied. There was no significant difference in the ΔFEV₁ (mL or %) with or without a spacer (MDI + spacer vs. MDI, mean ± SD, 365.1 ± 146.5 mL vs. 356.3 ± 131.1 mL, p = 0.696; and 21.4 ± 9.4% vs. 21.4 ± 9.5%, p = 0.968, respectively). When patients rinsed their mouth after inhalation, bronchodilatation was significantly less in those using an MDI alone compared with MDI + spacer (302.6 ± 116.5 mL vs. 367.6 ± 128.3 mL, p = 0.002; and 18.0% ± 7.9% vs. 21.7% ± 9.5%, p = 0.013, respectively). Conclusions. When patients correctly use an MDI, addition of a spacer does not significantly improve bronchodilatation. However, if the mouth is rinsed after inhalation, a spacer does yield better bronchodilatation. Our results suggest that systemic effects from bronchodilator inhalation may not be negligible.     

Poor Perception of Airway Obstruction in Children with Asthma

The aims of this study were to evaluate children's perception of asthma symptoms and to determine a clinically useful method for identifying poor patient perception of airway obstruction. Three methods were used to analyze the relationships among indices of lung function and perception of breathlessness in 35 children. Approximately half the children in our sample did not perceive either airway obstruction or bronchodilation. We propose that <20% improvement in visual analog scale scores post-bronchodilation may provide a simple index for identifying patients with poor perception of airway obstruction, who may be at risk for fatal or near-fatal asthma.     

Evaluation of Bedoradrine Sulfate (MN-221), a Novel,Highly Selective Beta2-Adrenergic Receptor Agonist for the Treatment of Asthma via Intravenous Infusion

Background. The number of hospitalizations or deaths due to asthma, most of which result from acute exacerbations of asthma, has remained the same for the past 20 years. MN-221 (bedoradrine sulfate) is a novel, highly selective beta₂- (β₂-) adrenergic agonist administered via intravenous (IV) infusion in development for the treatment for acute exacerbation of asthma. Objectives. Trial MN-221-CL-004 assessed the safety profile and preliminary efficacy of MN-221 in escalating doses in patients with stable mild-to-moderate asthma. Study MN-221-CL-005 assessed the safety profile and preliminary efficacy of MN-221 in patients with stable moderate-to-severe asthma when given as a fixed dose over 1- or 2- hr infusion. Methods. Two randomized, placebo-controlled clinical trials (n = 40) were performed to evaluate the pharmacokinetic (PK) and clinical effects of a novel, highly selective β₂-agonist, MN-221, via IV infusion. Safety evaluations included vital signs, adverse events (AEs), clinical laboratory parameters, and electrocardiogram results. Efficacy evaluation included measurement of forced expiratory volume in 1 second (FEV₁) and PK parameters were additionally monitored. The study was reviewed and approved by the Institutional Review Board at each site. Results. Adverse effects were mild or moderate and there were no serious AEs or deaths during the studies. The most frequently reported AEs were tremor, hypokalemia, and headache. There were no consistent dose-dependent effects of MN-221 on any safety parameters, with the exception of heart rate, which was not considered to be clinically significant and did not require any treatment. Moderate hypokalemia occurred once in one subject in the MN-221-CL-004 study and twice in one subject in the MN-221-CL-005 study and were transient and returned to normal range following single oral potassium chloride treatments. PK assessments indicated a linear response in MN-221 plasma concentrations for the doses evaluated. Dose escalation results showed that mean changes in FEV₁ from pre-infusion were significantly greater than placebo and an overall dose response was statistically significant (p < .0001). Post-infusion FEV₁ improvements appeared to plateau at the 30 μg/min dose level despite a higher peak plasma concentration at 60 μg/min. Dose-rate escalation results demonstrated greater mean increases in change in FEV₁ compared to the placebo group with the largest increase associated with the higher MN-221 dose rate and peak plasma concentration. Conclusions. The safety profile of MN-221 and evidence of dose- and plasma-concentration-related bronchodilation supports further clinical development and suggests the potential for clinical benefit without increased clinical risk, particularly for patients where inhaled or nebulized therapy is not adequate or possible. Trial registry name and registration number:Name: MN-221-CL-005Number: NCT00679263     

Effect of Dust Aerosol in Patients with Asthma

Objective. Sandstorms frequently cause adverse health effects especially in patients with asthma. The aim of our research was to explore the mechanism of sandstorm-induced asthmatic exacerbation by administering dust aerosol through an environmentally controlled exposure chamber. Methods. Four samples of soil (Ganganagar clay, Bikaner sand, Jaipur sand, and Ganganagar sand) were collected from three sandstorm-prone areas of Rajasthan, the desert state of India. Twenty patients with asthma, who had stable disease with a forced expiratory volume in first second (FEV₁) more than 70% of predicted, volunteered to participate in this randomized single-blind placebo-controlled crossover study. The four samples of dust and placebo were administered randomly on 5 study days. FEV₁ was measured for the next 60 minutes and the maximal decline in FEV₁ (ΔFEV₁) from baseline was measured. The samples of dust were also analyzed for particle size and adhesiveness. Results. The maximal decline in FEV₁ was observed 15 minutes post-exposure with all dust samples. Mean ΔFEV₁ was 0.69 ± 0.08 liters for Ganganagar clay, 0.52 ± 0.06 liters for Bikaner sand, 0.39 ± 0.07 liters for Jaipur sand, and 0.32 ± 0.04 liters for Ganganagar sand dust aerosol samples. Decline in FEV₁ correlated with volume of dust particles with size <10 μm (PM₁₀) and adhesiveness of the dust particles. Conclusion. Smaller-size sandstorm dust particles with higher adhesive properties have a greater potential of aggravating asthma.