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

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          Abstract

          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.

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          Most cited references23

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          Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations.

          The aim of the Task Force was to derive continuous prediction equations and their lower limits of normal for spirometric indices, which are applicable globally. Over 160,000 data points from 72 centres in 33 countries were shared with the European Respiratory Society Global Lung Function Initiative. Eliminating data that could not be used (mostly missing ethnic group, some outliers) left 97,759 records of healthy nonsmokers (55.3% females) aged 2.5-95 yrs. Lung function data were collated and prediction equations derived using the LMS method, which allows simultaneous modelling of the mean (mu), the coefficient of variation (sigma) and skewness (lambda) of a distribution family. After discarding 23,572 records, mostly because they could not be combined with other ethnic or geographic groups, reference equations were derived for healthy individuals aged 3-95 yrs for Caucasians (n=57,395), African-Americans (n=3,545), and North (n=4,992) and South East Asians (n=8,255). Forced expiratory value in 1 s (FEV(1)) and forced vital capacity (FVC) between ethnic groups differed proportionally from that in Caucasians, such that FEV(1)/FVC remained virtually independent of ethnic group. For individuals not represented by these four groups, or of mixed ethnic origins, a composite equation taken as the average of the above equations is provided to facilitate interpretation until a more appropriate solution is developed. Spirometric prediction equations for the 3-95-age range are now available that include appropriate age-dependent lower limits of normal. They can be applied globally to different ethnic groups. Additional data from the Indian subcontinent and Arabic, Polynesian and Latin American countries, as well as Africa will further improve these equations in the future.
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            Exploring the relevance and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study

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              Measurement of FEF25-75% and FEF75% does not contribute to clinical decision making.

              The aim of this study was to determine the added value of measuring the forced expiratory flow at 25-75% of forced vital capacity (FVC) (FEF25-75%) and flow when 75% of FVC has been exhaled (FEF75%) over and above the measurement of the forced expiratory volume in 1 s (FEV1), FVC and FEV1/FVC ratio. We used spirometric measurements of FEV1, FVC and FEF25-75% from 11 654 white males and 11 113 white females, aged 3-94 years, routinely tested in the pulmonary function laboratories of four tertiary hospitals. FEF75% was available in 8254 males and 7407 females. Predicted values and lower limits of normal, defined as the fifth percentile, were calculated for FEV1, FVC, FEV1/FVC ratio, FEF25-75% and FEF75% using prediction equations from the Global Lung Function Initiative. There was very little discordance in classifying test results. FEF25-75% and FEF75% were below the normal range in only 2.75% and 1.29% of cases, respectively, whereas FEV1, FVC and FEV1/FVC ratio were within normal limits. Airways obstruction went undetected by FEF25-75% in 2.9% of cases and by FEF75% in 12.3% of cases. Maximum mid-expiratory flow and flow towards the end of the forced expiratory manoeuvre do not contribute usefully to clinical decision making over and above information from FEV1, FVC and FEV1/FVC ratio.
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                Author and article information

                Contributors
                Journal
                Heliyon
                Heliyon
                Heliyon
                Elsevier
                2405-8440
                06 October 2023
                October 2023
                06 October 2023
                : 9
                : 10
                : e20744
                Affiliations
                [a ]Rehabilitation Health Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
                [b ]Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham, UK
                [c ]Respiratory Therapy Department, College of Applied Medical Sciences, King Saud Bin Abdul-Aziz University for Health Sciences, Al Ahsa, Saudi Arabia
                [d ]Department of Lung Function and Sleep, University Hospitals Birmingham NHS Foundation Trust, Edgbaston, Birmingham, B15 2GW, UK
                Author notes
                []Corresponding author. Rehabilitation Health Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia. malmeshari@ 123456ksu.edu.sa
                Article
                S2405-8440(23)07952-5 e20744
                10.1016/j.heliyon.2023.e20744
                10585212
                37867812
                1da2f516-03cf-447c-8f1e-d9d72f9391b5
                © 2023 The Authors. Published by Elsevier Ltd.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 July 2023
                : 23 September 2023
                : 5 October 2023
                Categories
                Research Article

                spirometry,z-score,standardised residual,small airways,fef25-75,mmef

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