Combining small airway parameters with conventional parameters obtained during spirometry to diagnose airflow obstruction: A cross-sectional study.

BACKGROUND AND OBJECTIVE: The use of small airway parameters generated by spirometry, namely forced expiratory flow between 25% and 75% of forced vital capacity (FVC) (FEF25%-75%) and forced expiratory flow at 50% and 75% of FVC (FEF50% and FEF75%, respectively), is widely discussed. We evaluated the importance of these spirometric parameters in a large Chinese population. METHODS: We conducted a cross-sectional observational study in which spirometry and bronchodilator responsiveness (BDR) data were collected in a healthcare centre from May 2021 to August 2022 and in a tertiary hospital from January 2017 to March 2022. Discordance was assessed between the classification of test results by the large airway parameters of forced expiratory volume in 1 second (FEV1) and FEV1/FVC ratio and by the small airway parameters of FEF25%-75%, FEF75% and FEF50%. The predictive power of Z-scores of spirometric parameters for airflow limitation and BDR was assessed using receiver operating characteristic curves. RESULTS: Our study included 26,658 people. Among people with a normal FVC (n = 14,688), 3.7%, 4.5% and 3.6% of cases exhibited normal FEV1/FVC ratio but impaired FEF25%-75%, FEF75% and FEF50%, respectively, while 6.8%-7.0% of people exhibited normal FEV1 but impaired FEF25%-75%, FEF75% and FEF50%. Using the Z-scores of combining both large and small airway parameters in spirometry showed the best area under the curve for predicting airflow limitation (0.90; 95% CI 0.87-0.94) and predicting BDR (0.72; 95% CI 0.71-0.73). CONCLUSION: It is important to consider both large and small airway parameters in spirometry to avoid missing a diagnosis of airflow obstruction.

The impact of occupational exposure to crystalline silica dust on respiratory function (airway obstruction and FEF25-75) in the French general population.

INTRODUCTION: Although several studies have studied the relationship between occupational exposure to crystalline silica dust and respiratory mortality, few have examined the relationship with impairments in respiratory function and the exposure threshold triggering spirometric monitoring in exposed workers. The objective of the present study was to evaluate the impact of exposure to crystalline silica dust on respiratory function. METHODS: We included 1428 male participants (aged 40 to 65) recruited from the French general population, at random from electoral rolls, in the cross-sectional ELISABET study and for whom data on forced expiratory flow-volume curve indices z-scores (calculated using the Global Lung Function Initiative 2012 equations) and exposure (via a questionnaire) were available. A cumulative exposure index (CEI) for crystalline silica dust (CEIsilica, expressed in mg.m-3.year) was calculated using the Matgéné occupational exposure matrix. RESULTS: 293 of the 1428 participants (20.52%) reported exposure to silica dust. We found that the adjusted z-scores for the forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) ratio decreased significantly as CEIsilica increased. After adjustment, the adjusted z-scores for FEV1/FVC (ß: -0.426 (95% confidence interval (CI): -0.792, -0.060) per 1 mg m-3.year increment) and the mean forced expiratory flow between 25 and 75% of the forced vital capacity (FEF25-75) (ß: -0.552 (95% CI: -0.947, -0.157)) were significantly lower in the participants with CEIsilica ≥1 mg m-3.year than in non-exposed participants. The likelihoods of having airway obstruction (odds ratio (OR): 3.056 (95% CI: 1.107, 7.626)) or having an impaired FEF25-75 (OR: 4.305 (95% CI: 1.393, 11.79)) were also significantly higher in participants with CEIsilica ≥1 mg m-3.year. CONCLUSION: Our results emphasize the importance of spirometry-based monitoring in workers exposed to more than 1 mg m-3.year of crystalline silica dust, in order to identify small airway obstruction or airway obstruction as early as possible.

The role of small airway function parameters in preschool asthmatic children.

BACKGROUND: Small airways are the major sites of inflammation and airway remodeling in all severities of asthma patients. However, whether small airway function parameters could reflect the airway dysfunction feature in preschool asthmatic children remain unclear. We aim to investigate the role of small airway function parameters in evaluating airway dysfunction, airflow limitation and airway hyperresponsiveness (AHR). METHODS: Eight hundred and fifty-one preschool children diagnosed with asthma were enrolled retrospectively to investigate the characteristics of small airway function parameters. Curve estimation analysis was applied to clarify the correlation between small and large airway dysfunction. Spearman's correlation and receiver-operating characteristic (ROC) curves were employed to evaluate the relationship between small airway dysfunction (SAD) and AHR. RESULTS: The prevalence of SAD was 19.5% (166 of 851) in this cross-sectional cohort study. Small airway function parameters (FEF25-75%, FEF50%, FEF75%) showed strong correlations with FEV1% (r = 0.670, 0.658, 0.609, p<0.001, respectively), FEV1/FVC% (r = 0.812, 0.751, 0.871, p<0.001, respectively) and PEF% (r = 0.626, 0.635, 0.530, p<0.01, respectively). Moreover, small airway function parameters and large airway function parameters (FEV1%, FEV1/FVC%, PEF%) were curve-associated rather than linear-related (p<0.001). FEF25-75%, FEF50%, FEF75% and FEV1% demonstrated a positive correlation with PC20 (r = 0.282, 0.291, 0.251, 0.224, p<0.001, respectively). Interestingly, FEF25-75% and FEF50% exhibited a higher correlation coefficient with PC20 than FEV1% (0.282 vs. 0.224, p = 0.031 and 0.291 vs. 0.224, p = 0.014, respectively). ROC curve analysis for predicting moderate to severe AHR showed that the area under the curve (AUC) was 0.796, 0.783, 0.738, and 0.802 for FEF25-75%, FEF50%, FEF75%, and the combination of FEF25-75% and FEF75%, respectively. When Compared to children with normal lung function, patients with SAD were slightly older, more likely to have a family history of asthma and airflow obstruction with lower FEV1% and FEV1/FVC%, lower PEF% and more severe AHR with lower PC20 ( all p<0.05). CONCLUSION: Small airway dysfunction is highly correlated with large airway function impairment, severe airflow obstruction and AHR in preschool asthmatic children. Small airway function parameters should be utilized in the management of preschool asthma.

Impact of Biologic Therapy on the Small Airways Asthma Phenotype.

The small airways dysfunction (SAD) asthma phenotype is characterised by narrowing of airways < 2 mm in diameter between generations 8 and 23 of the bronchial tree. Recently, this has become particularly relevant as measurements of small airways using airway oscillometry for example, are strong determinants of asthma control and exacerbations in moderate-to-severe asthma. The small airways can be assessed using spirometry as forced expiratory flow rate between 25 and 75% of forced vital capacity (FEF25-75) and has been deemed more accurate in detecting small airways dysfunction than forced expiratory volume in 1 s (FEV1). Oscillometry as the heterogeneity in resistance between 5 and 20 Hz (R5-R20), low frequency reactance at 5 Hz (X5) or area under the reactance curve between 5 Hz and the resonant frequency can also be used to assess the small airways. The small airways can also be assessed using the multiple breath nitrogen washout (MBNW) test giving rise to values including functional residual capacity, lung clearance index and ventilation distribution heterogeneity in the conducting (Scond) and the acinar (Sacin) airways. The ATLANTIS group showed that the prevalence of small airways disease in asthma defined on FEF25-75, oscillometry and MBNW all increased with progressive GINA asthma disease stages. As opposed to topical inhaler therapy that might not adequately penetrate the small airways, it is perhaps more intuitive that systemic anti-inflammatory therapy with biologics targeting downstream cytokines and upstream epithelial anti-alarmins may offer a promising solution to SAD. Here we therefore aim to appraise the available evidence for the effect of anti-IgE, anti-IL5 (Rα), anti-IL4Rα, anti-TSLP and anti-IL33 biologics on small airways disease in patients with severe asthma.

Use of FEF25-75% to Guide IgG Dosing to Protect Pulmonary Function in CVID.

Immunoglobulin replacement therapy (IGRT) can protect against lung function decline in CVID. We tested whether increasing IgG dosage was beneficial in patients who exhibited a decline in forced expiratory flow at 25-75% (FEF25-75%) even though they were receiving IgG doses within the therapeutic range. Of 189 CVID patients seen over 12 years, 38 patients met inclusion criteria, were seen on ≥ 3 visits, and demonstrated a ≥ 10% decrease in FEF25-75% from visits 1 to 2. FEF25-75%, forced expiratory flow at 1 s (FEV1), and FEV1/FVC at visit 3 were compared among those with non-dose adjustment (non-DA) versus additional IgG dose adjustment (DA). Three FEF25-75% tiers were identified: top (> 80% predicted), middle (50-80%), and bottom (< 50%). DA and non-DA groups did not differ in clinical infections or bronchodilator use, although the non-DA group tended to use more antibiotics. In the top, normal tier, FEF25-75% increased in DA, but the change did not achieve statistical significance. In the middle moderate obstruction tier, visit 3 FEF25-75% increased among DA but not non-DA sets (11.8 ± 12.4%, p = 0.003 vs. 0.3 ± 9.9%, p = 0.94). Improvement in FEV1/FVC at visit 3 was also significant among DA vs. non-DA (7.2 ± 12.4%, p = 0.04 vs. - 0.2 ± 2.7%, p = 0.85). In the bottom, severe tier, FEF25-75% was unchanged in DA (- 0.5 ± 5.2%, p = 0.79), but increased in non-DA (5.1 ± 5.2%, p = 0.02). Among IGRT CVID patients with moderate but not severe obstruction as assessed by spirometry, increasing IgG dosage led to an increase in FEF25-75% and FEV1/FVC.

Mepolizumab effectiveness on small airway obstruction, corticosteroid sparing and maintenance therapy step-down in real life.

BACKGROUND: Mepolizumab (MEP) has been recently introduced to treat severe eosinophilic asthma. Trials have demonstrated a significant effectiveness in this asthma phenotype. We evaluated MEP efficacy on lung function, symptoms, asthma exacerbations, biologic markers, steroid dependence and controller treatment level in real-life. METHODS: We retrospectively analyzed 134 severe asthmatics (61 males; mean age 58.3 ± 11; mean FEV1%:72 ± 21), treated with MEP for at least 6 months (mean duration:10.9 ± 3.7 months). RESULTS: FEV1% improved significantly after MEP. Mean FEF25-75 also increased from 37.4 ± 25.4% to 47.2 ± 27.2% (p < 0.0001). Mean baseline blood eosinophil level was 712 ± 731/µL (8.4 ± 5.2%) decreasing to 151 ± 384/µL (1.6 ± 1.6%) (p < 0.0001), FENO levels decreased likewise. MEP treatment also led to a significant ACT improvement (mean pre:14.2 ± 4.4; mean post:20.5 ± 28) and exacerbations significantly fell from 3.8 ± 1.9 to 0.8 ± 1.1 (p < 0.0001). 74% of patients were steroid-dependent before MEP. 45.4% and 46.4% of them showed a suspension and dose reduction respectively (p < 0.0001). A significant number reduced also ICS doses. Only 67% of subjects used SABA as needed before MEP, falling to 20% after MEP. About 40% of patients highlighted a maintenance therapy step-down. Subjects showing an omalizumab treatment failure before MEP had a similar positive response when compared with omalizumab untreated patients. CONCLUSION: In real-life, MEP improved significantly all outcomes even small airway obstruction, suggesting its possible role also in distal lung region treatment. Furthermore, it demonstrated its high effectiveness in OC/ICS-sparing, in reducing SABA as needed and in stepping-down maintenance therapy. MEP is a valid alternative for patients with previous omalizumab treatment failure.

Spirometric reference values in heathy Chinese adults in Taiwan: The secular changes and comparison with other Asian populations.

BACKGROUND/PURPOSE: Although the lung function test has played an important role in respiratory care for a long time, valid spirometry reference values in the Chinese population in Taiwan remain to be elucidated. METHODS: 2963 healthy Taiwanese subjects aged 21 to 88 years (1765 males, 59.6%) from February 2015 to February 2017 were enrolled. The subjects attempted to meet the 2005 American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines when performing forced expiratory spirograms. We would like to establish the spirometry predictive equations for forced expiratory volume (FEV1), forced vital capacity (FVC), FEV1/FVC, and lower limit of normal (LLN) in Taiwan and compare with other Asian populations. RESULTS: We established the spirometry predictive equations using a linear model for the entire population, using age and height as independent variables, which best predicted all spirometry parameters for sea level and highland subjects. We found that the values of FEV1 and FVC for the Taiwanese subjects in our study were systematically lower than those reported in South Korea, Japan, and China, but higher than the values in Yang's 1993 and Pan's 1997 Taiwan study. CONCLUSION: This study addressed the up-to-date spirometry reference equations and values for a healthy adult Chinese population in Taiwan.

Could routine spirometry suggest sensitisation in the military medicine setting?

INTRODUCTION: Providing evidence of sensitisation is the formal requirement for allergy diagnosis. The aim of this study was to evaluate whether spirometry may be able to predict sensitisation in a representative cohort of Italian Navy military personnel. METHODS: 2043 (1875 men, 168 women, mean age 28.35±11.6 years) Italian Navy military personnel were enrolled into this study. Spirometry and skin prick testing were performed to predict sensitisation. RESULTS: Sensitisation, assessed by skin prick test, was documented in 658 (32.2%) subjects. Impaired forced expiratory flow at the 25% and 75% of the pulmonary volume (FEF25-75) as demonstrated on spirometry was detected in 82 subjects, of whom 69 were sensitised (P<0.0001). Impaired FEF25-75 was significantly associated with sensitisation (OR 7.43; 95% CI 4.04 to 14.66; P<0.0001). DISCUSSION: The findings of this study suggest that impaired FEF25-75 may predict sensitisation in this cohort of Italian Navy personnel. This outcome is relevant in the military medical setting, as it could allow early identification of subjects with subclinical asthma.

Forced midexpiratory flow between 25% and 75% of forced vital capacity is associated with long-term persistence of asthma and poor asthma outcomes.

BACKGROUND: Whether small-airway obstruction contributes to the long-term evolution of asthma remains unknown. OBJECTIVES: Our aim was to assess whether the level of forced midexpiratory flow between 25% and 75% of forced vital capacity (FEF25-75) was associated with the persistence of current asthma over 20 years and the subsequent risk for uncontrolled asthma independently of FEV1. METHODS: We studied 337 participants (142 children and 225 adults) with current asthma (asthma attacks or treatment in the past 12 months) recruited to the Epidemiological Study on the Genetics and Environment of Asthma (EGEA1) and followed up at the 12- and 20-year surveys. Persistent current asthma was defined by current asthma reported at each survey. A lung function test and a methacholine challenge test were performed at EGEA1 and EGEA2. Adjusted odds ratios (ORs) were estimated for FEF25-75 decreased by 10% of predicted value. RESULTS: A reduced level of FEF25-75 at EGEA1 increased the risk of long-term asthma persistence (adjusted OR, 1.14; 95% CI, 1.00-1.29). In children the association remained significant after further adjustment for FEV1 and in participants with FEV1 of greater than 80% of predicted value. A reduced FEF25-75 level at EGEA1 was significantly associated with more severe bronchial hyperresponsiveness (P < .0001) and with current asthma a decade later, with an association that tended to be stronger in those with (adjusted OR, 1.44; 95% CI, 1.14-1.81) compared with those without (adjusted OR, 1.21; 95% CI, 1.05-1.41) asthma exacerbation. CONCLUSION: Our analysis is the first to suggest that small-airway obstruction, as assessed based on FEF25-75, might contribute to the long-term persistence of asthma and the subsequent risk for poor asthma outcomes independently from effects of the large airways.

Pulmonary outcome in former preterm, very low birth weight children with bronchopulmonary dysplasia: a case-control follow-up at school age.

OBJECTIVE: To assess and compare long-term pulmonary outcomes in former preterm-born, very low birth weight (VLBW) children with and without bronchopulmonary dysplasia (BPD) born in the surfactant era. STUDY DESIGN: Pulmonary function tests (ie, spirometry, body plethysmography, and gas transfer testing) were performed in children with a history of VLBW and BPD (n = 28) and compared with a matched preterm-born VLBW control group (n = 28). Medical history was evaluated by questionnaire. RESULTS: At time of follow-up (mean age, 9.5 years), respiratory symptoms (36% vs 8%) and receipt of asthma medication (21% vs 0%) were significantly more frequent in the preterm-born children with previous BPD than in those with no history of BPD. The children with a history of BPD had significantly lower values for forced expiratory volume in 1 second (z-score -1.27 vs -0.4; P = .008), forced vital capacity (z-score -1.39 vs -0.71 z-score; P = .022), and forced expiratory flow rate at 50% of forced vital capacity (z-score -2.21 vs -1.04; P = .048) compared with the preterm control group. CONCLUSION: Preterm-born children with a history of BPD are significantly more likely to have lung function abnormalities, such as airway obstruction and respiratory symptoms, at school age compared with preterm-born children without BPD.

May T1 diabetes mellitus protect from asthma?

BACKGROUND: Type 1 diabetes mellitus (T1DM) may be associated with allergy. It was previously reported that >20% of children with T1DM had allergic rhinitis (AR), but none was asthmatic. This finding was surprising as allergic rhinitis is frequently associated with asthma and asthma prevalence is about 10% of the general paediatric population. Thus, it was hypothesized that T1DM could protect from asthma. OBJECTIVES: The aim of this preliminary study was to evaluate the pulmonary function and the response to bronchodilation testing in children, suffering from T1DM with associated AR, comparing them with a control group of children with AR alone. METHODS: Twenty children with T1DM and AR were compared with 59 children with AR alone; spirometry and bronchodilation testing were performed in all patients. RESULTS: There were no statistically significant differences in both "at baseline" and after bronchodilation testing about FVC, FEV1, and FEF25-75 values. However, changes in "post-bronchodilator" values of FEF25-75 (ΔFEF25-75) were significantly higher in children with AR alone than in children with T1DM and AR (p=0.04). CONCLUSIONS: This preliminary study could sustain the hypothesis that T1DM in children suffering also from AR might exert a protective effect of preventing the possible evolution in asthma.

Small airways dysfunction: The importance of utilising Z-scores to define MMEF abnormalities in clinical practice.

Background: The small airways comprise the largest cross-sectional area of the lungs, however, assessing and reporting abnormalities for this region of the bronchial tree has been practically and scientifically uncertain. Methods: Using routinely collected spirometry data for patients with either asthma or COPD, the accuracy of % predicted values for defining small airways dysfunction was assessed. A z-score of ≤ -1.645 of the maximal-mid expiratory flow (MMEF) was used as the gold standard for defining abnormality in the small airways. Results: Records of 3396 patients were included in the analysis. The false positive (FP) rates were 24.6 %, 16.1 %, 11.5 %, or 7.9 % when the % predicted value of 80 %, 70 %, 65 %, or 60 % were used, respectively. Sex, age, and BMI were associated with FP rates. Males were more likely to be categorised as FP with odds ratio (OR) between 1.10 and 1.49 across % predicted groups. Age was associated with FP rates with an OR between 1.01 and 1.08. The BMI was also associated with FP rates with an OR of 1.03 across all % predicted groups. Assessing the association of age groups with FP rate showed that those above 60 years old were more likely to be categorised as FP with an OR between 1.23 and 73.2 compared to those less than 30 years old. Conclusion: When assessing the small airways in clinical practice or for scientific purposes, the % predicted values overestimate the actual impairment leading to FP interpretation. Utilising z-score values are recommended to assess the small airways using the spirometric index, MMEF.

Pulmonary Function Tests in Childhood Asthma: Which indices are Better for Assessment of Severity?

OBJECTIVE: To study pulmonary function tests in childhood asthma and to determine which indices are better for assessment of severity. METHODS: This was a hospital-based, cross-sectional study. All consecutive children aged between 5 and 15 y with mild and severe persistent asthma were enrolled. Children in whom diagnosis of asthma was doubtful and those with chronic lung disease or suppurative lung disease were excluded. Diagnosis and classification was based on GINA guidelines. Age-/sex-matched controls who did not have history of wheezing any time in the past were selected. Detailed spirometry was performed on all children enrolled using RMS HELIOS 401. RESULTS: A total of 144 children were enrolled in the study (48 children in each group, i.e., control, mild and severe). Mean age of the study population was 9.06 ± 2.604 y with M:F ratio of 1.9:1. Mean percent of predicted values of FEV1, FVC, FEV1/FVC, FEF25-75, and PEFR in the control group was 94.83, 92.63, 103.25, 73.90, and 93.60; in the mild group was 90.58, 83.52, 111.10, 76.50, and 92.00; and in the severe group 57.56, 62.83, 92.85, 40.15, and 62.12, respectively. Values of all the indices decreased with increase in severity. FEV1 (95% CI: 0.884 to 0.971) having the highest correlation coefficient (-0.652) with respect to severity of asthma and FEV1/FVC having the least (-0.202). FEF25-75 (95% CI: 0.652 to 0.803) having a higher area under the curve, was a better spirometric parameter in predicting mild asthma. CONCLUSION: FEV1 was better index for assessing severity of asthma and FEF25-75 better in predicting mild asthma.

The Practical Role of FEF25-75 in Young Patients with Allergic Rhinitis.

Allergic rhinitis (AR) is a relevant risk factor asthma as it may frequently precede asthma onset. There is evidence that lung function may be early impaired in AR patients. In this regard, the forced expiratory flow at 25%-75% of vital capacity (FEF25-75) could be a reliable marker of bronchial impairment in AR. Therefore, the present study investigated the practical role of FEF25-75 in young people with AR. The parameters included history, body mass index (BMI), lung function, bronchial hyperresponsiveness (BHR), and fractional exhaled nitric oxide (FeNO). This cross-sectional study included 759 patients (74 females and 685 males, mean age of 29.2 years) suffering from AR. The study demonstrated a significant association between low FEF25-75 values and BMI (OR 0.80), FEV1 (OR 1.29), FEV1/FVC (OR 1.71), and BHR (OR 0.11). Stratifying the patients on the basis of the presence (or absence) of BHR, sensitization to house dust mites (OR 1.81), AR duration (OR 1.08), FEF25-75 (OR 0.94), and FeNO (OR 1.08) were associated with BHR. Stratifying patients based on high FeNO values (>50 ppb), BHR was associated with high FeNO (OR 39). In conclusion, the present study showed that FEF25-75 was associated with low FEV1 and FEV1/FVC and BHR in AR patients. Therefore, spirometry should be considered in the long-term workup of patients with allergic rhinitis as impaired FEF25-75 might suggest an initial progression toward asthma.

Early COPD diagnosis and treatment: A case report.

Chronic obstructive pulmonary disease (COPD) refers to a group of widely diffuse diseases that cause airflow blockage characterized by persistent respiratory symptoms such as dyspnea, chronic cough, recurrent wheezing, chronic sputum production, and progressive restricted airflow associated with exacerbations. COPD is the third leading cause of death worldwide and can only be treated not cured. Pulmonary function tests do not permit the identification of initial obstructive airways disease. Forced expiratory flow (FEF25-75), which calculates obstruction severity at small and medium bronchial airways levels, allows an early COPD diagnosis. We report a 72-year-old ex-smoker male not exposed to occupational risk with symptoms suggesting early COPD. Baseline pulmonary function tests were normal, except FEF25-75. The patient did not respond to the first 6 months of treatment with long-acting muscarinic antagonist (LAMA), whereas he showed a clear clinical and FEF25-75 response to 1-year treatment with LAMA associated with long-acting ß2 agonist (LABA). This clinical case report highlights the usefulness of FEF25-75 evaluation in early COPD diagnosis and monitoring and confirms the efficacy of LAMA-LABA association for small airways obstruction treatment.

Long-Term Efficacy and Safety Among Patients With Severe Eosinophilic Asthma Treated With Mepolizumab and Its Effect on Small Airways.

BACKGROUND: The major problem at the Cleveland Allergy and Asthma Center was the need for additional therapy for severe eosinophilic asthma patients who were steroid-dependent or required frequent bursts of prednisone. OBJECTIVES: The objectives of this study were to determine the efficacy of monthly mepolizumab (MP) injections up to 6½ years using Asthma Control Quesitonnaire-7 (ACQ-7), forced expiratory volume in 1 second (FEV1), forced expiratory flow at 25% to 75% (FEF25%-75%) overall and among super-responders, and to understand whether FEF25%-75% is an effective parameter to evaluate MP efficacy. METHODS: We reviewed the charts of 67 patients with severe eosinophilic asthma and compared the results between 47 super-responders and the rest of the cohort regarding ACQ-6, ACQ-7, eosinophils, FEV1, and FEF25%-75%. The groups of super-responders and all other patients were described with respect to initial and current values of the study end points using medians and 25th and 75th percentiles. Changes from the initial to the current values in the study end points were measured using percent changes. The Wilcoxon signed rank test was used within each group to test the null hypothesis of 0 median percent change. RESULTS: After 6½ years, there were no significant changes in FEV1. The FEF25%-75%, had a significant median percent increase of 40% among the super-responders (P < .001), which was substantially higher (P = .026) than the median percent increase of 13.8% observed among all other patients. CONCLUSIONS: The use of MP up to 6½ years was safe and effective, with significant changes to ACQ-7 and FEF25%-75% associated with MP treatment, but not the FEV1. A higher magnitude of changes was observed among super-responders than the rest of the cohort. Changes in FEF25%-75% were more meaningful than changes in FEV1 in evaluating pulmonary function responsiveness of severe eosinophilic asthma to MP.

Baseline Spirometry as a Predictor of Positive Methacholine Challenge Testing for Exertional Dyspnea.

BACKGROUND: There are several tests recommended by the American Thoracic Society (ATS) to evaluate for airway hyper-responsiveness (AHR), one of which is methacholine challenge testing (MCT). Few studies have examined the correlation of baseline spirometry to predict AHR in MCT, especially in the younger, relatively healthy military population under clinical evaluation for symptoms of exertional dyspnea. The study aim was to retrospectively correlate baseline spirometry values with MCT responsiveness. METHODS: This study is a retrospective review of all MCT performed at Brooke Army Medical Center/Wilford Hall Medical Center over a 12-y period; all completed studies were obtained from electronic databases. The following parameters were analyzed from the studies: baseline FEV1, FVC, FEV1/FVC, mid-expiratory flow (FEV25-75%), FEV25-75%/FVC. Studies were categorized based on baseline obstruction, restriction, FEF25-75% lower limit of normal, and response to bronchodilator testing (if completed); these values were compared based on methacholine reactivity and severity. RESULTS: Methacholine challenge studies (n = 1,933) were reviewed and categorized into reactive (n = 577) and nonreactive (n = 1,356) as determined by ATS guidelines. The mean baseline FEV1 (% predicted) with MCT reactivity was 88.0 ± 13.0% versus no MCT reactivity was 92.7 ± 13.0% (P < .001). The mean baseline FVC (% predicted) was 93.1 ± 13.7% versus 95.3 ± 13.5% (P < .001). The mean baseline FEV25-75% (% predicted) was 80.0 ± 22.1% versus 89.0 ± 23.4% (P < .001). Based on partition analysis, methacholine reactivity was most prevalent with baseline obstruction, n = 115 (43%), and in the absence of obstruction, when the FEF25-75% (% predicted) was below 0.70, n = 111 (40%). The negative predictive value with normal spirometry was 73%. CONCLUSIONS: The analysis of baseline spirometry prior to MCT proved useful in the evaluation of exertional dyspnea in a military population. The presence of airways obstruction (FEV1/FVC < lower limit of the normal range) followed by a reduction in FEV25-75% < 70% predicted showed a positive correlation with underlying AHR. In patients with exertional dyspnea and normal baseline spirometry, the use of the FEF25-75% may be a useful surrogate measurement to predict reactivity during MCT and consideration for additional testing or treatment.

Forced Expiratory Flow at 25%-75% Links COPD Physiology to Emphysema and Disease Severity in the SPIROMICS Cohort.

BACKGROUND: Forced expiratory volume in 1 second (FEV1) is central to the diagnosis of chronic obstructive pulmonary disease (COPD) but is imprecise in classifying disease burden. We examined the potential of the maximal mid-expiratory flow rate (forced expiratory flow rate between 25% and 75% [FEF25%-75%]) as an additional tool for characterizing pathophysiology in COPD. OBJECTIVE: To determine whether FEF25%-75% helps predict clinical and radiographic abnormalities in COPD. STUDY DESIGN AND METHODS: The SubPopulations and InteRediate Outcome Measures In COPD Study (SPIROMICS) enrolled a prospective cohort of 2978 nonsmokers and ever-smokers, with and without COPD, to identify phenotypes and intermediate markers of disease progression. We used baseline data from 2771 ever-smokers from the SPIROMICS cohort to identify associations between percent predicted FEF25%-75% (%predFEF25%-75%) and both clinical markers and computed tomography (CT) findings of smoking-related lung disease. RESULTS: Lower %predFEF25-75% was associated with more severe disease, manifested radiographically by increased functional small airways disease, emphysema (most notably with homogeneous distribution), CT-measured residual volume, total lung capacity (TLC), and airway wall thickness, and clinically by increased symptoms, decreased 6-minute walk distance, and increased bronchodilator responsiveness (BDR). A lower %predFEF25-75% remained significantly associated with increased emphysema, functional small airways disease, TLC, and BDR after adjustment for FEV1 or forced vital capacity (FVC). INTERPRETATION: The %predFEF25-75% provides additional information about disease manifestation beyond FEV1. These associations may reflect loss of elastic recoil and air trapping from emphysema and intrinsic small airways disease. Thus, %predFEF25-75% helps link the anatomic pathology and deranged physiology of COPD.

Inhaled albuterol increases estimated ventilatory capacity in nonasthmatic children without and with obesity.

Forced mid-expiratory flow (i.e., isoFEF25-75) may increase with a short-acting ß2-agonist in nonasthmatic children without bronchodilator responsiveness. This could also increase estimated ventilatory capacity along mid-expiration (V̇Ecap25-75), especially in vulnerable children with obesity who exhibit altered breathing mechanics. We estimated V̇Ecap25-75 pre- and post-albuterol treatment in 8-12yo children without (n = 28) and with (n = 46) obesity. A two-way ANOVA was performed to determine effects of an inhaled bronchodilator (pre-post) and obesity (group) on isoFEF25-75 and V̇Ecap25-75. There was no group by bronchodilator interaction or main group effect on outcome variables. However, a significant main effect of the bronchodilator was detected in spirometry parameters, including a substantial increase in isoFEF25-75 (17.1 ±â€¯18.0 %) and only a slight (non-clinical) but significant increase in FEV1 (2.4 ±â€¯4.3 %). V̇Ecap25-75 significantly increased with albuterol (+11.7 ±â€¯10.6 L/min; +15.8 ±â€¯13.9 %). These findings imply potentially important increases in ventilatory reserve with a bronchodilator in nonasthmatic children without and with obesity, which could potentially influence respiratory function at rest and during exercise.

FEF25-75% Is a More Sensitive Measure Reflecting Airway Dysfunction in Patients with Asthma: A Comparison Study Using FEF25-75% and FEV1.

BACKGROUND: Reduced forced expiratory flow between 25% and 75% of vital capacity percent predicted (FEF25-75%) representing small airway dysfunction (SAD) was associated with asthma development and progression. OBJECTIVE: To investigate whether FEF25-75% was superior to forced expiratory volume in 1 second in predicted (FEV1%) in reflecting asthma features in adult patients. METHODS: A retrospective spirometry dataset comprising 1801 adult patients with confirmed asthma and a subgroup of 332 patients having detailed clinical data were used to explore the association of FEF25-75% and/or FEV1% with clinical features of asthma. RESULTS: Of the 1801 subjects, FEV1% and FEF25-75% ranged from 136.8% to 10.2% and 127.3% to 3.1%, respectively. FEF25-75% < 65% was present in 1,478 (82.07%) of patients. FEF25-75% was strongly correlated with matched FEV1% (r = 0.900, P < .001). FEF25-75% and FEV1% were both correlated with airway hyperresponsiveness (r = 0.436, P < .001; r = 0.367, P < .001), asthma control test score (r = 0.329, P < .001; r = 0.335, P < .001), and sputum eosinophil count (r = -0.306, P < .001; r = -0.307, P < .001). Receiver-operating characteristic curves showed that FEF25-75% had greater value in predicting severe asthma (area under the curve: 0.84 vs 0.81, P = .018), airflow obstruction (0.97 vs 0.89, P < .001), and severe bronchial hyperresponsiveness (0.74 vs 0.69, P = .012) as compared with FEV1%. Patients with SAD (FEF25-75% < 65%) in the presence of normal FEV1% exhibited higher sputum eosinophil counts and had an increased dosage of daily inhaled corticosteroids (P < .001 and P = .010) than patients with normal lung function and their FEF25-75% values correlated with sputum eosinophil count (r = -0.419, P = .015), but not FEV1%. CONCLUSION: FEF25-75% represented small airway function and was more sensitive at reflecting airway hyperresponsiveness, inflammation, and disease severity as compared with FEV1% in patients with asthma. Our data suggest further assessment of FEF25-75% in asthma management, particularly for those with SAD who present normal FEV1%.