Next Article in Journal
EUS-Guided Biopsy with a Novel Puncture Biopsy Forceps Needle—Feasibility Study
Next Article in Special Issue
Multiparametric MRI and Radiomics in Prostate Cancer: A Review of the Current Literature
Previous Article in Journal
When Familial Hearing Loss Means Genetic Heterogeneity: A Model Case Report
Previous Article in Special Issue
Structured Reporting of Lung Cancer Staging: A Consensus Proposal
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Diagnostics
Volume 11
Issue 9
10.3390/diagnostics11091637
diagnostics-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Lung Function Decline in Adult Asthmatics—A 10-Year Follow-Up Retrospective and Prospective Study

by
Salvatore Bucchieri
1,
Pietro Alfano
1,
Palma Audino
1,
Fabio Cibella
1,
Giovanni Fazio
2,*,
Salvatore Marcantonio
3 and
Giuseppina Cuttitta
1
1
Institute for Biomedical Research and Innovation, National Research Council of Italy, Via U.La Malfa, 153, 90146 Palermo, Italy
2
Triolo Zanca Clinic, Piazza Fonderia, 23, 90133 Palermo, Italy
3
Quality, Planning and Strategic Support Area, University of Palermo, Piazza Marina, 61, 90133 Palermo, Italy
*
Author to whom correspondence should be addressed.
Diagnostics 2021, 11(9), 1637; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11091637
Submission received: 19 August 2021 / Revised: 2 September 2021 / Accepted: 3 September 2021 / Published: 7 September 2021
(This article belongs to the Special Issue Advances in Diagnostic Medical Imaging)
Browse Figures
Review Reports Versions Notes

Abstract

:
Asthma may have an impact on lung function decline but conflicting results are reported in forced expiratory volume in one second (FEV1) decline. We aimed to describe the changes in FEV1 in lifelong non-smoking adult asthmatic outpatients during a 10-year follow-up comparing years 1–5 (1st period) with years 6–10 (2nd period) to assess factors affecting these changes. A total of 100 outpatients performed spirometry every 3 months during a 10-year survey. FEV1/Ht3 slope values of the 2nd period reduced significantly respect to the 1st period (p < 0.0001). FEV1 slopes of years 1–5 and 6–10 were inversely associated with FEV1 at enrolment (p = 0.02, p = 0.01, respectively). Reversibility and variability FEV1 showed a significant effect on the 1st period slopes (p = 0.01 and p < 0.04, respectively). Frequent exacerbators in the 1st year had steeper FEV1/Ht3 slopes in the 1st period (p = 0.01). The number of subjects using higher doses of ICS was significantly lower at the 10th years respect to the 5th and the 1st year (p < 0.001, p = 0.003, respectively). This study shows that FEV1 decline in treated adult asthmatics non-smokers, over 10-year follow-up, is not constant. In particular, it slows down over time, and is influenced by FEV1 at enrolment, reversibility, variability FEV1 and exacerbation score in the 1st year.

1. Introduction

Conflicting results exist regarding lung function decline rates in asthmatics: in forced expiratory volume in one second (FEV1), rates range from almost normal [1,2] to those expected in chronic obstructive pulmonary disease (COPD) [3,4]. Asthma may have a significant impact on lung function decline [5,6] and recent studies suggest that long-term treatment with inhaled steroids may decrease FEV1 decline [7,8]. However, if little is known about other factors associated with FEV1 decline in adult asthmatics, the relationship of the characteristics of such patients and biomarkers of progression for airflow limitation, a functional consequence of airway remodelling, is considered important in the management of asthma [9]. We previously reported that longer disease duration may decrease the decline rate in asthmatics during a five-year period [10]: this interaction may add to the effects of asthma treatment.
We studied a sample of 100 non-smoker asthmatic outpatients followed-up by spirometry every 3 months during a 10-year survey. The purpose of this study was to evaluated the longitudinal FEV1 changes during this period, comparing years 1–5 (1st period) with years 6–10 (2nd period) also determining possible factors affecting functional decline.

2. Methods

A database was established in 2001. In this database were recorded the longitudinal data over the present: patients’ demographic characteristics, asthma symptoms based on Global Initiative for Asthma (GINA) guidelines [11], exacerbations and treatment details including frequency of consultation, rescue therapy, hospitalization, type and dose of asthma medications, respiratory variables relevant to the first visit and their subsequent visits. Data for this study are from the National Research Council of Palermo, a public primary care institution comprising a pneumological clinical. A total of 1930 patients were recorded in the database over the period 2001–2012.
Inclusion criteria were: consecutive lifelong non-smoking asthmatics followed-up over a 10-year period in an outpatient asthma clinic; a follow-up visit every three months for every year of observation, inclusive of pulmonary evaluation with spirometry. We enrolled 100 non-smoking asthmatics (aged 18–66 years, 41 M). The anthropometric, clinical, and functional characteristics at enrolment are presented in Table 1. FEV1 rate of decline compared with other studies are presented in Table 2.
At enrolment, personal history of bronchial asthma was confirmed by FEV1 reversibility (FEV1,rev%) after inhalation of 400 μg salbutamol [11,12]. In the presence of suggestive asthma symptoms without immediate reversibility, subjects underwent a course of oral steroids (OS): a new functional assessment was performed and long-term reversibility computed.
Skin prick tests were performed with a panel including the most common aeroallergens, plus positive and negative control (Stallergenes Italia S.r.l), following EAACI recommendations. Allergic sensitization was indicated by at least one positive skin prick test [13].
During the follow-up, subjects underwent clinical and spirometric evaluations every three months and therapeutic recommendations were repeated. Patients were treated according to GINA guidelines [11]. In case of exacerbation, patients could receive telephonic counselling or unscheduled visit.
An inhaled corticosteroid (ICS) score was computed on the basis of daily ICS dose in µg: Low ≤ 500; Moderate > 500 and ≤1000; High > 1000. Cycles of short-term OS were used for computing the asthma exacerbations. The number of exacerbations during the 1st, 5th, and 10th years of follow-up were recorded. Subjects with a number of OS ≥ 2 were identified as frequent exacerbators, while those with OS < 2 were infrequent exacerbators.
FEV1 variability, as expression of bronchial responsiveness [14] was calculated at the 1st, 5th, and 10th year of follow-up, following the formula: (FEV1,max − FEV1,min)/FEV1,pred × 100. FEV1,max and FEV1,min were the maximum and minimum FEV1 recorded during the 1st, 5th, and 10th years of follow-up, and FEV1,pred was the corresponding individual predicted FEV1.
To compare all subjects independently of height, individual FEV1 data were normalized for the subject’s height at the third power (FEV1/Ht3, L/m3/y) [15]. For each year of follow-up, the best FEV1 measure in each 6-month period was analysed [16]. Thus, in the follow-up, 20 FEV1/Ht3 values resulted for each subject. The relationship between FEV1/Ht3 values as dependent variable and year (or year fractions) as independent variable was treated by linear regression analysis to obtain individual slopes to the 1st (slope FEV1/Ht3-1st period) and 2nd period (slope FEV1/Ht3-2nd period). The individual differences between slopes were calculated as differences between the slope of the 6th–10th year period and slope of the 1st–5th year period (∆slope FEV1/Ht3).
Slopes were tested against the investigated variables (unless otherwise indicated, continuous variables were dichotomized using the median value): gender, age at enrolment (<47.5 and ≥47.5 years), age of disease onset (<29 and ≥29 years), body mass index (BMI, <26 and ≥26 Kg/m2), FEV1 at enrolment (as continuous variable), FEV1 variability (<11.3% and ≥11.3%), reversibility (FEV1,postBD ≥ 12% respect to pre-bronchodilator FEV1), disease duration (<13 years and ≥13 years), allergic sensitization (Yes/No), rhinitis (Yes/No), ICS score (Low, Moderate, High) and exacerbation score (frequent/infrequent exacerbators).The study was approved by the Local Institutional Ethics Committee (authorization reference number 7/2013).

Statistical Analysis

Differences in frequency distribution of variables were evaluated by χ2 test, median differences, for not normally distributed variables, were evaluated by U Mann–Whitney tests for unpaired sample and by Wilcoxon test for paired sample.
Correlation between continuous variables was investigated using Spearman Rank Correlation.
All computations were performed by StatView statistical software package (SAS Institute, Cary, NC, USA). A probability level of p < 0.05 was selected as statistically significant.

3. Results

3.1. FEV1 Decline

The FEV1/Ht3 slope values for the two periods were not significantly different for gender (Mann–Whitney U test). All FEV1/Ht3 slopes in the 1st period showed negative values whereas in the 2nd period the slopes were significantly less negative than 1st period slopes or positive (Wilcoxon test, p < 0.0001). The median FEV1/Ht3 slope computed on the whole population sample was −0.010 L/m3/year (range −0.079 to −0.0004) for years 1–5 and −0.006 L/m3/year (range −0.038 to +0.038) for years 6–10 (Figure 1). In years 1–5, FEV1 loss was 42.5 mL/year, computed for a 1.62 m tall subject (median height of sample); it was 25.5 mL/year, in years 6–10. A significant inverse relationship was found between ∆slope FEV1/Ht3 and slope FEV1/Ht3 1–5 year (p < 0.0001 Spearman Rank Correlation) (Figure 2).

3.2. Determinants of FEV1 Decline

A significant inverse correlation was found between the FEV1 slopes of years 1–5 and FEV1 at enrolment, expressed as percent of predicted (p = 0.02, Spearman Rank Correlation); such a correlation was also found for years 6–10 (p = 0.01) (Figure 3, Panels A and B).
Subjects with FEV1 reversibility showed steeper FEV1 slopes in years 1–5 with respect to subjects without reversibility (p = 0.01, Mann–Whitney U test) but no significant effect of reversibility was observed on FEV1 slopes for years 6–10 (Figure 4).
FEV1 variability at the 1st year had a significant effect on lung function decline in the 1st period: subjects with FEV1 variability ≥12% showed significantly steeper slopes in years 1–5 (p < 0.04, Mann–Whitney U test) compared to subjects with lower variability. No significant effect on FEV1 slopes for years 6–10 was observed for subjects with high and low FEV1 variability at 1st year (Figure 5).
A significant reduction in FEV1 variability was observed during the follow-up: median FEV1 variability at the 5th and 10th years was significantly lower than that of the 1st year (p < 0.0001, respectively, Wilcoxon test). In addition, a significant difference was found between the 5th and 10th years (p = 0.02, Wilcoxon test). (Figure 6).
Analysing exacerbation score, the prevalence of frequent exacerbators was 12%, 15% and 10%, at 1st, 5th and 10th year, respectively, with a significant difference in frequency distribution between 1st and 10th years (p = 0.004, χ2), and between 5th and 10th years (p = 0.001, χ2). No significant difference between 1st and 5th years was found. Frequent exacerbators in the 1st year had steeper FEV1/Ht3 slopes in the 1st period (p = 0.01, Mann–Whitney U test) but no effect was found on 2nd period slopes. Analysing ICS scores across the follow-up, we found that the number of subjects using higher doses of ICS was significantly lower at the 10th years respect to the 5th and to the 1st year (p < 0.0001, p = 0.003; χ2, respectively) and at the 5th year respect to 1st year (p < 0.02; χ2), with a complementary increase of subjects using lower doses in the corresponding years. (Figure 7). BMI had no significant effect of age at enrolment. Disease duration, or age of disease onset was observed on FEV1 slopes in two periods. Similarly, gender, allergic sensitization and rhinitis showed no effect on FEV1 decline.

4. Discussion

This longitudinal study was carried out on 100 lifelong non-smoking adult asthmatic outpatients with a well-defined clinical and functional diagnosis of bronchial asthma. They had a clinical and pulmonary function evaluations every 3 months during a 10-year follow-up.
Our results indicate that FEV1 decline in treated asthmatics over the follow-up period was not constant, but rather slowed over time. Whereas a steeper decline was observed during the 1st period, the decline was much slower in the 2nd period. Moreover, while FEV1 decline in the 1st period was influenced by reversibility, FEV1 at enrolment, FEV1 variability in the 1st year, and exacerbations in the 1st year, in the second period it was not. Furthermore, we found an overall decrease over the time in the number of subjects using high/moderate daily doses of inhaled steroids.
When decline was separately computed in the two periods, it showed a striking intraindividual difference: mean FEV1 loss was 42.5 mL/year in the 1st period and 25.5 mL/year per year in the 2nd. Thus, mean FEV1 decline in the 2nd period was 54% lower with respect to the 1st period. Our study produces different results with respect to previous papers. Peat et al. in an 18-year population health survey reported a loss of 50 mL/year in males (average height 1.70 m) with asthma and a loss of 35 mL/year in normal subjects [15]. Moreover, Lange et al., in a 15-year follow-up study [17] found a loss of 38 mL/year in adult asthmatics and 22 mL/year in non-asthmatics. In a 10-year longitudinal study, Burrows et al. (1) found a 70 mL/year mean overall rate of decline in COPD subjects and 65 mL/year in asthmatics. Contoli [18] more recently, in a 5-year follow-up, reported a rate of FEV1 decline of 50 mL/year in asthmatics with fixed airflow obstruction and of 18 mL/year in asthmatics with reversible airflow obstruction.
We supposed that important factors could have influenced the differences in the extent of FEV1 loss, such as: (I) incorrect diagnosis (mainly asthma vs. COPD) due to limitations of selected methods (e.g., self-reported diagnosis, questionnaire); (II) inclusion of functional values collected during exacerbations; (III) few functional measurements over the follow-up; (IV) analysis performed on the entire follow-up period; (V) variable effect of pharmacological control of bronchoconstriction over time; and (VI) inclusion of current and former smokers.
We tried to overcome these factors by means of (I) a well-defined asthma diagnosis; (II) four spirometries per year, to minimize the “learning” effect and decrease the risk of decline overestimation due to changes in disease control over time; (III) excluding both current and former smokers; (IV) separate analysis of the 1st and 2nd period of the follow-up to highlight the effect of pharmacological control over time.
All patients were lifelong non-smokers in order to avoid the interaction and detrimental effects of smoking [19,20] on the FEV1 decline [21]. Moreover, a typical trajectory of age-related FEV1 decline were related to a change in the lifestyle related risk factors, BMI and smoking, these have significantly impact aging-related decline of lung function [22].
In agreement with a previous study [23], we found an inverse relationship between FEV1 decline in the 1st period and FEV1 at enrolment, the same result was obtained for FEV1 decline in the 2nd period: a steeper FEV1 decline in subjects with higher baseline FEV1 values. We surmised that the decline can no longer be progressive after the FEV1 had previously dropped to a considerable extent.
Acute salbutamol reversibility was not associated with FEV1 decline. This lack of association could be explained by the presence of airway inflammation. In fact, when considering long term reversibility (evaluated after trial with OS), we found that subjects with reversibility showed a steeper FEV1 decline in the 1st period, but not in the 2nd. Ulrik et al. reported similar results observing that a high degree of reversibility was associated with a steeper functional decline in asthmatics over the following 10 years [21]. Vollmer et al. reported that the response to an inhaled bronchodilator correlated with the rate of FEV1 decline only in subjects classified as having bronchial hyperresponsiveness [24]. In our study, using FEV1 variability at 1st year, as an expression of bronchial hyperresponsiveness, we found that it was the strongest predictor of lung function decline in the 1st period but not in the 2nd, agreeing with previous studies showing that higher airway responsiveness was responsible for accelerated FEV1 decline [25,26,27].
We hypothesized that greater variability of lung function over time is a marker of poorly controlled asthma, thus significantly affecting the rate of FEV1 decline. We found that the reduction of FEV1 decline over time was associated with a progressive reduction in FEV1 variability over time. In agreement with Metha et al., we suggest that the reduction in bronchial hyperresponsiveness produced and maintained by a regular ICS treatment may be responsible for the changes [28]
Moreover, a well-defined effect of ICS on the rate of decline in lung function has been reported, while the effect of bronchodilators was less conclusive, so we choose to analyse only the effect of ICS [29,30].
Observational studies, showed a less pronounced decline in FEV1 in asthmatics taking ICS compared to those not receiving them [17]. Moreover, an early and regular ICS, introduced when symptoms are mild, was expected to prevent lung function worsening suggesting that ICS could reduce the intensity of airway remodelling and thus produce slower lung function decline [8,31]
Our results demonstrate that the step-down approach to long-term asthma therapy, grants asthma control along with a positive effect on lung function decline. In fact, despite the large increase in the number of subjects assuming a low ICS dose in the 2nd period with respect to 1st one (19 to 38%), the overall FEV1 decline resulted less negative [32].
Previous studies have reported a strong effect of ICS to prevent asthma exacerbations [33,34], accordingly, we found a reduction of number of high exacerbators over the follow-up period. We surmised that the significant reduction of FEV1 loss in years 6–10 with respect to years 1–5 could be due to early and regular ICS treatment of our patients [29]. We did not find any effect of disease duration on rate of decline in both periods. It is possible that asthmatics may have an excessive functional decline prior to the time of diagnosis, and also in the first years following asthma onset [3]. Accordingly, the studied subjects had a wide range of disease duration, and we could not clearly document which treatment had been adopted.
In the last decades a growing interest was reported in the lung microbiota. Previous studies reported a shift in the lung microbiota during lung diseases, in particular in asthma [35]. Moreover, the lung microbiota is more diverse and abundant in some subjects with asthma [35,36,37,38,39]. It remains a matter of debate whether we should be talking about dysbiosis, stable colonization, or infections of the lungs. Furthermore, the function and causal role of this shift in the lung microbiota in the outcome of asthma remain unclear [40]. Unfortunately, we did not study this aspect in our patients.
Ulrik and Lange showed that the rate of FEV1 decline was higher in subjects with recent asthma onset compared to subjects with chronic asthma, as well as in men compared to women [5,6]. Controversies exist relevant to this effect on FEV1 decline [41,42] We did not find any influence of gender on FEV1 decline in either the 1st or 2nd 5-year period. The gender difference in FEV1 loss reported in previous studies could be explained by women’s increased susceptibility to the lung-damaging effects of cigarette smoking and to development of chronic airway obstruction among asthmatics [19,43,44]. Therefore, we have chosen to include only lifelong non-smokers patients. Furthermore, our patients showed a comparable reversibility airflow obstruction that could explain the similar rate of FEV1 decline over time.
With regard to the influence of age on lung function decline in asthma, we did not find any influence of age on FEV1 decline either in the 1st or 2nd period. Similar results were reported by Peat et al. in a long follow-up study on asthmatics [15]. Conversely, in other studies, aging was found to be associated with a steeper decline in FEV1 [8,20].
In our study, BMI did not influence FEV1 decline. Conversely, Marcon A et al. [23] had reported a faster FEV1 decline in the non-obese compared with the obese: this finding could be due to a lower baseline FEV1 and the process of decline may no longer be progressive after FEV1 had previously dropped a considerable extent. This different result could be due to presence of more obese subjects in their sample (BMI > 30).
In agreement with previous studies [15,41] we found that allergic sensitization does not appear to be a determinant of changes in the rate of functional decline in asthma, suggesting that inflammatory processes in the airways of patients with asthma may run their course, irrespective of allergic status.

5. Conclusions

The present study shows that the rate of FEV1 decline over ten years follow-up in non-smoking adults treated for asthma proves not to be constant when calculated separately in 2 consecutive 5-year periods. In fact, it reduces over time, slowing down until it reaches an FEV1 rate of decline comparable to normal subjects. In the 1st 5-year period, FEV1 reversibility, higher FEV1 variability and exacerbations are determinant factors, while in the 2nd period those factors are no longer determinant.
These findings suggest the possible role of early, continuous, and regular long-term treatment with ICS in reducing number of high exacerbators over the follow-up period, the intensity of airway remodelling and thus produce slower lung function decline in asthma patients [45].

Author Contributions

Conceptualization, G.C., S.B. and F.C.; data curation, G.C.; Formal analysis, G.C., P.A. (Pietro Alfano), P.A. (Palma Audino). and. S.M.; methodology, G.C. and F.C.; project administration, G.C. and G.F.; supervision, G.C., S.B., P.A. (Pietro Alfano) and G.F.; validation, G.C., S.B., S.M. and G.F.; visualization, G.C., S.B. and P.A. (Palma Audino); writing—original draft, G.C., S.B. and F.C.; writing—review and editing, G.C., S.B., P.A. (Pietro Alfano) and G.F. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by Institute of Research and Biomedical Innovation (IRIB), Italian National Council (CNR), Palermo, Italy.

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Ethics Committee (authorization reference number 7/2013).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

Primary data are available upon request.

Acknowledgments

The authors acknowledge the patients and their families.

Conflicts of Interest

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

References

  1. Burrows, B.; Bloom, J.W.; Traver, G.A.; Cline, M.G. The course and prognosis of different forms of chronic airways obstruction in a sample from the general population. N. Engl. J. Med. 1987, 317, 1309–1314. [Google Scholar] [CrossRef] [PubMed]
  2. Torén, K.; Schiöler, L.; Lindberg, A.; Andersson, A.; Behndig, A.F.; Bergström, G.; Blomberg, A.; Caidahl, K.; Engval, J.E.; Eriksson, M.J.; et al. The ratio FEV1/FVC and its association to respiratory symptoms—A Swedish general population study. Clin. Physiol. Funct. Imaging 2021, 41, 181–191. [Google Scholar] [CrossRef]
  3. Kanner, R.E.; Renzetti, A.D., Jr.; Klauber, M.R.; Smith, C.B.; Golden, C.A. Variables associated with changes in spirometry in patients with obstructive lung diseases. Am. J. Med. 1979, 67, 44–50. [Google Scholar] [CrossRef]
  4. Ørts, L.M.; Bech, B.H.; Lauritzen, T.; Carlsen, A.H.; Sandbæk, A.; Løkke, A. Lung function in adults and future burden of obstructive lung diseases in a long-term follow-up. NPJ Prim. Care Respir. Med. 2020, 30, 10. [Google Scholar] [CrossRef] [Green Version]
  5. Ulrik, C.S.; Lange, P. Decline of lung function in adults with bronchial asthma. Am. J. Respir. Crit. Care Med. 1994, 150, 629–634. [Google Scholar] [CrossRef]
  6. Lange, P.; Parner, J.; Vestbo, J.; Schnohr, P.; Jensen, G.A. 15-year follow-up study of ventilatory function in adults with asthma. N. Engl. J. Med. 1998, 339, 1194–1200. [Google Scholar] [CrossRef]
  7. Raissy, H.H.; Kelly, H.W.; Harkins, M.; Szefler, S.J. Inhaled Corticosteroids in Lung Diseases. Am. J. Respir. Crit. Care Med. 2013, 187, 798–803. [Google Scholar] [CrossRef] [Green Version]
  8. Shimoda, T.; Obase, Y.; Kishikawa, R.; Iwanaga, T. Impact of Inhaled Corticosteroid Treatment on 15-Year Longitudinal Respiratory Function Changes in Adult Patients with Bronchial Asthma. Int. Arch. Allergy Immunol. 2013, 162, 323–329. [Google Scholar] [CrossRef]
  9. Kanemitsu, Y.; Matsumoto, H.; Mishima, M. Factors contributing to an accelerated decline in pulmonary function in asthma. Allergol. Int. 2014, 63, 181–188. [Google Scholar] [CrossRef] [Green Version]
  10. Cibella, F.; Cuttitta, G.; Bellia, V.; Bucchieri, S.; D’Anna, S.; Guerrera, D.; Bonsignore, G. Lung function decline in bronchial asthma. Chest 2002, 122, 1944–1948. [Google Scholar] [CrossRef] [Green Version]
  11. WHO/NHLBI Workshop Report. National Institutes of Health, National Heart, Lung and Blood Institute. Global Strategy for Asthma Management and Prevention. Publication Number 95-3659. 1995. Available online: http://www.ginasthma.org (accessed on 7 February 2014).
  12. American Thoracic Society. Standardization of Spirometry,1994 Update. Am. J. Respir. Crit. Care Med. 1995, 152, 1107–1136. [Google Scholar] [CrossRef] [PubMed]
  13. The European Academy of Allergology and Clinical Immunology. Position paper: Allergen standardization and skin tests. Allergy 1993, 48, 48–82. [Google Scholar] [CrossRef]
  14. Bellia, V.; Cibella, F.; Cuttitta, G.; Scichilone, N.; Mancuso, G.; Vignola, A.M.; Bonsignore, G. Effect of age upon airway obstruction and reversibility in adult asthmatics. Chest 1998, 114, 1336–1342. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  15. Peat, J.; Woolcock, A.; Cullen, K. Rate of decline of lung function in subjects with asthma. Eur. J. Respir. Dis. 1987, 70, 171–179. [Google Scholar]
  16. Burrows, B.; Lebowitz, M.D.; Camilli, A.E.; Knudson, R.J. Longitudinal changes in forced expiratory volume in one second in adults. Methodologic considerations and findings in healthy nonsmokers. Am. Rev. Respir. Dis. 1986, 133, 974–980. [Google Scholar] [CrossRef] [PubMed]
  17. Lange, P.; Scharling, H.; Ulrik, C.S.; Vestbo, J. Inhaled corticosteroids and decline of lung function in community residents with asthma. Thorax 2006, 61, 100–104. [Google Scholar] [CrossRef] [Green Version]
  18. Contoli, M.; Baraldo, S.; Marku, B.; Casolari, P.; Marwick, J.A.; Turato, G.; Romagnoli, M.; Caramori, G.; Saetta, M.; Fabbri, L.M. Fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease: 5-year follow-up. J. Allergy Clin. Immunol. 2010, 125, 830–837. [Google Scholar] [CrossRef]
  19. Xu, X.; Weiss, S.T.; Rijcken, B.; Schouten, J.P. Smoking, changes in smoking habits, and rate of decline in FEV1: New insight into gender differences. Eur. Respir. J. 1994, 7, 1056–1061. [Google Scholar] [CrossRef]
  20. Mohamed Hoesein, F.A.; Zanen, P.; Boezen, H.M.; Groen, H.J.M.; Van Ginneken, B.; de Jong, P.A.; Postma, D.S.; Lammers, J.W.J. Lung function decline in male heavy smokers relates to baseline airflow obstruction severity. Chest 2012, 142, 1530–1538. [Google Scholar] [CrossRef]
  21. Ulrik, C.S.; Backer, V.; Dirksen, A. A 10 year follow up of 180 adults with bronchial asthma: Factors important for the decline in lung function. Thorax 1992, 47, 14–18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  22. Van Oostrom, S.H.; Engelfriet, P.M.; Verschuren, W.M.; Schipper, M.; Wouters, I.M.; Boezen, M.; Smit, H.A.; Kerstjens, H.A.M.; Picavet, H.S.J. Aging-related trajectories of lung function in the general population—The Doetinchem Cohort Study. PLoS ONE 2018, 13, e0197250. [Google Scholar] [CrossRef]
  23. Marcon, A.; Corsico, A.; Cazzoletti, L.; Bugiani, M.; Accordini, M.S.; Almar, E.; Cerveri, I.; Gislason, D.; Gulsvik, A.; Janson, C.; et al. Therapy and Health Economics Group of the European Community Respiratory Health Survey. Body mass index, weight gain, and other determinants of lung function decline in adult asthma. J. Allergy Clin. Immunol. 2009, 123, 1069–1974. [Google Scholar] [CrossRef]
  24. Vollmer, W.M.; Johnson, L.R.; Buist, A.S. Relationship of response to a bronchodilator and decline in forced expiratory volume in one second in population studies. Am. Rev. Respir. Dis. 1985, 132, 1186–1193. [Google Scholar] [CrossRef]
  25. Rijcken, B.; Schouten, J.P.; Xu, X.; Rosner, B.; Weiss, S.T. Airway hyperresponsiveness to histamine associated with accelerated decline in FEV1. Am. J. Respir. Crit. Care Med. 1995, 151, 1377–1382. [Google Scholar] [CrossRef] [PubMed]
  26. Juusela, M.; Pallasaho, P.; Sarna, S.; Piirilä, P.; Lundbäck, B.; Sovijärvi, A. Bronchial hyperresponsiveness in an adult population in Helsinki: Decreased FEV1, the main determinant. Clin. Respir. J. 2013, 7, 34–44. [Google Scholar] [CrossRef] [Green Version]
  27. O’Connor, G.T.; Sparrow, D.; Weiss, S.T. A prospective longitudinal study of methacholine airway responsiveness as a predictor of pulmonary-function decline: The Normative Aging Study. Am. J. Respir. Crit. Care Med. 1995, 152, 87–92. [Google Scholar] [CrossRef] [PubMed]
  28. Mehta, V.; Stokes, J.R.; Berro, A.; Romero, F.A.; Casale, T.B. Time-dependent effects of inhaled corticosteroids on lung function, bronchial hyperresponsiveness, and airway inflammation in asthma. Ann. Allergy Asthma Immunol. 2009, 103, 31–37. [Google Scholar] [CrossRef]
  29. Carter, P.M.; Heinly, T.L.; Yates, S.W.; Lieberman, P.L. Asthma: The irreversible airways disease. J. Investig. Allergol. Clin. Immunol. 1997, 7, 566–571. [Google Scholar]
  30. Prakash, Y.S.; Halayko, A.J.; Gosens, R.; Panettieri, R.A., Jr.; Camoretti-Mercado, B.; Penn, R.B. An official American Thoracic Society research statement: Current challenges facing research and therapeutic advances in airway remodeling. Am. J. Respir. Crit. Care Med. 2017, 195, e4–e19. [Google Scholar] [CrossRef]
  31. Janson, C. The importance of airway remodelling in the natural course of asthma. Clin. Respir. J. 2010, 4, 28–34. [Google Scholar] [CrossRef] [PubMed]
  32. O’Byrne, P.M.; Jenkins, C.; Bateman, E.D. The paradoxes of asthma management: Time for a new approach? Eur. Respir. J. 2017, 50, 1701103. [Google Scholar] [CrossRef] [Green Version]
  33. Barnes, P.J. Efficacy of inhaled corticosteroids in asthma. Allergy Clin. Immunol. 1998, 102, 531–538. [Google Scholar] [CrossRef]
  34. Lee, J.; Huvanandana, J.; Foster, J.M.; Reddel, H.K.; Abramson, M.J.; Thamrin, C.; Hew, M. Dynamics of inhaled corticosteroid use are associated with asthma attacks. Sci. Reports. 2021, 11, 14715. [Google Scholar] [CrossRef]
  35. Hooks, K.B.; O’Malley, M.A. Dysbiosis and its discontents. MBio 2017, 8, e01492-17. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  36. Hilty, M.; Burke, C.; Pedro, H.; Cardenas, P.; Bush, A.; Bossley, C.; Davies, J.; Ervine, A.; Poulter, L.; Pachter, L.; et al. Disordered microbial communities in asthmatic airways. PLoS ONE 2010, 5, e8578. [Google Scholar] [CrossRef] [Green Version]
  37. Huang, Y.J.; Nelson, C.E.; Brodie, E.L.; DeSantis, T.Z.; Baek, M.S.; Liu, J.; Woyke, T.; Allgaier, M.; Bristow, J.; Wiener-Kronish, J.P.; et al. National Heart, Lung, and Blood Institute. Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma. J. Allergy Clin. Immunol. 2011, 127, 372–381. [Google Scholar] [CrossRef] [Green Version]
  38. Goleva, E.; Jackson, L.P.; Harris, J.K.; Robertson, C.E.; Sutherland, E.R.; Hall, C.F.; Good, J.T., Jr.; Gelfand, E.W.; Martin, R.J.; Leung, D.Y. The effects of airway microbiome on corticosteroid responsiveness in asthma. Am. J. Respir. Crit. Care Med. 2013, 188, 1193–1201. [Google Scholar] [CrossRef] [Green Version]
  39. Fujimura, K.E.; Lynch, S.V. Microbiota in allergy and asthma and the emerging relationship with the gut microbiome. Cell Host Microbe 2015, 17, 592–602. [Google Scholar] [CrossRef] [Green Version]
  40. Barcik, W.; Boutin, R.C.; Sokolowska, M.; Finlay, B.B. The role of lung and gut microbiota in the pathology of asthma. Immunity 2020, 52, 241–255. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  41. Peat, J.K.; Woolcock, A.J.; Cullen, K. Decline of lung function and development of chronic airflow limitation: A longitudinal study of non-smokers and smokers in Busselton, Western Australia. Thorax 1990, 45, 32–37. [Google Scholar] [CrossRef] [Green Version]
  42. Amelink, M.; de Nijs, S.B.; Berger, M.; Weersink, E.J.; ten Brinke, A.; Bel, E.H. Non-atopic males with adult-onset asthma are at risk of persistent airflow limitation. Clin. Exp. Allergy 2012, 42, 769–774. [Google Scholar] [CrossRef] [PubMed]
  43. Backman, H.; Jansson, S.A.; Stridsman, C.; Muellerova, H.; Wurst, K.; Hedman, L.; Lindberg, A.; Rönmark, E. Chronic airway obstruction in a population-based adult asthma cohort: Prevalence, incidence and prognostic factors. Respir. Med. 2018, 138, 115–122. [Google Scholar] [CrossRef] [PubMed]
  44. Chen, Y.; Horne, S.L.; Dosman, J.A. Increased susceptibility to lung dysfunction. Am. Rev. Respir Dis. 1991, 143, 1224–1230. [Google Scholar] [CrossRef]
  45. Panhuysen, C.I.; Vonk, J.M.; Koëter, G.H.; Schouten, J.P.; van Altena, R.; Bleecker, E.R.; Postma, D.S. Adult patients may outgrow their asthma. A 25-year follow-up study. Am. J. Respir. Crit. Care Med. 1997, 155, 1267–1272. [Google Scholar] [CrossRef] [PubMed]
Diagnostics 11 01637 g001 550
Figure 1. Slope values of relationships between height-adjusted FEV1 and time (L/m3/year), separately for years 1–5 and 6–10. Bars indicate (from the bottom to the top) 10th, 25th, 50th (median), 75th and 90th percentiles. Values below 10th and above 90th percentiles are plotted as circles. A significant difference was found (p < 0.0001, Wilcoxon test).
Figure 1. Slope values of relationships between height-adjusted FEV1 and time (L/m3/year), separately for years 1–5 and 6–10. Bars indicate (from the bottom to the top) 10th, 25th, 50th (median), 75th and 90th percentiles. Values below 10th and above 90th percentiles are plotted as circles. A significant difference was found (p < 0.0001, Wilcoxon test).
Diagnostics 11 01637 g001
Diagnostics 11 01637 g002 550
Figure 2. Relationship between the individual differences between the slope of the 6th–10th year period and slope of the 1st–5th year period (∆slope FEV1/Ht3) and slope FEV1 years 1–5. A significant inverse correlation was found (p < 0.0001, Spearman Rank Correlation).
Figure 2. Relationship between the individual differences between the slope of the 6th–10th year period and slope of the 1st–5th year period (∆slope FEV1/Ht3) and slope FEV1 years 1–5. A significant inverse correlation was found (p < 0.0001, Spearman Rank Correlation).
Diagnostics 11 01637 g002
Diagnostics 11 01637 g003 550
Figure 3. Relationships between slope values of relationships between height-adjusted FEV1 and time (L/m3/year) for years 1–5 (Panel A) and for years 6–10 (Panel B) and FEV1 at enrolment (% of predicted). Both correlations were significant (p = 0.02 and p = 0.01, respectively, Spearman Rank Correlation).
Figure 3. Relationships between slope values of relationships between height-adjusted FEV1 and time (L/m3/year) for years 1–5 (Panel A) and for years 6–10 (Panel B) and FEV1 at enrolment (% of predicted). Both correlations were significant (p = 0.02 and p = 0.01, respectively, Spearman Rank Correlation).
Diagnostics 11 01637 g003
Diagnostics 11 01637 g004 550
Figure 4. Slope values of relationships between height-adjusted FEV1 and time (L/m3/year) during years 1–5 and years 6–10, separately for subjects with or without FEV1 reversibility at enrolment. Bars indicate (from the bottom to the top) 10th, 25th, 50th (median), 75th and 90th percentiles. Values below 10th and above 90th percentiles are plotted as circles. In years 1–5 subjects with FEV1 reversibility at enrolment showed significantly lower slope values (p = 0.01, Mann–Whitney U-test). No significant effect of reversibility was observed on FEV1 slopes for years 6–10.
Figure 4. Slope values of relationships between height-adjusted FEV1 and time (L/m3/year) during years 1–5 and years 6–10, separately for subjects with or without FEV1 reversibility at enrolment. Bars indicate (from the bottom to the top) 10th, 25th, 50th (median), 75th and 90th percentiles. Values below 10th and above 90th percentiles are plotted as circles. In years 1–5 subjects with FEV1 reversibility at enrolment showed significantly lower slope values (p = 0.01, Mann–Whitney U-test). No significant effect of reversibility was observed on FEV1 slopes for years 6–10.
Diagnostics 11 01637 g004
Diagnostics 11 01637 g005 550
Figure 5. Slope values of relationships between height-adjusted FEV1 and time (L/m3/year) during years 1–5 and years 6–10, separately for groups of FEV1 variability at 1st year. Bars indicate (from the bottom to the top) 10th, 25th, 50th (median), 75th and 90th percentiles. Values below 10th and above 90th percentiles are plotted as circles. In years 1–5 subjects with FEV1 variability at 1st year showed significantly lower slope values (p < 0.04, Mann–Whitney U-test). No significant effect of variability was observed on FEV1 slopes for years 6–10.
Figure 5. Slope values of relationships between height-adjusted FEV1 and time (L/m3/year) during years 1–5 and years 6–10, separately for groups of FEV1 variability at 1st year. Bars indicate (from the bottom to the top) 10th, 25th, 50th (median), 75th and 90th percentiles. Values below 10th and above 90th percentiles are plotted as circles. In years 1–5 subjects with FEV1 variability at 1st year showed significantly lower slope values (p < 0.04, Mann–Whitney U-test). No significant effect of variability was observed on FEV1 slopes for years 6–10.
Diagnostics 11 01637 g005
Diagnostics 11 01637 g006 550
Figure 6. FEV1 variability (in percent of predicted), separately for 1st, 5th, and 10th years. Bars indicate (from the bottom to the top) 10th, 25th, 50th (median), 75th, and 90th percentiles. Values below 10th and above 90th percentiles are plotted as circles. Significant differences were found between 1st and 5th years, between 1st and 10th years and between 5th and 10th years (Wilcoxon test).
Figure 6. FEV1 variability (in percent of predicted), separately for 1st, 5th, and 10th years. Bars indicate (from the bottom to the top) 10th, 25th, 50th (median), 75th, and 90th percentiles. Values below 10th and above 90th percentiles are plotted as circles. Significant differences were found between 1st and 5th years, between 1st and 10th years and between 5th and 10th years (Wilcoxon test).
Diagnostics 11 01637 g006
Diagnostics 11 01637 g007 550
Figure 7. Prevalence of subjects, for each inhaled corticosteroid (ICS) score during the follow-up period. A Scheme of 10th and 5th years (p < 0.0001, χ2), between 10th and 1st years (p = 0.003, χ2), and between 5th and 1st years (p < 0.02, χ2).
Figure 7. Prevalence of subjects, for each inhaled corticosteroid (ICS) score during the follow-up period. A Scheme of 10th and 5th years (p < 0.0001, χ2), between 10th and 1st years (p = 0.003, χ2), and between 5th and 1st years (p < 0.02, χ2).
Diagnostics 11 01637 g007
Table
Table 1. Anthropometric, clinical, and pulmonary functional characteristics at enrolment, according to sex.
Table 1. Anthropometric, clinical, and pulmonary functional characteristics at enrolment, according to sex.
Females (No 59)Males (No 41)p Value
Age at enrolment49 (35–55)43 (30–53)0.04
Body mass index25 (22–30)27 (23–28)N.S.
Age of disease onset33 (19–43)24 (12–38)N.S.
Disease duration12 (7–21)15 (5–20)N.S.
FEV1 at enrolment85 (70–97)80 (70–91)N.S.
FVC at enrolment105 (93–114)98 (96–109)N.S.
FEV1/FVC at enrolment (absolute, %)69 (61–75)68 (58–73)N.S.
FEV1 rev, %16 (9–33)23 (12–51)N.S.
Allergic sensitization (No, %)41 (69)28 (68)N.S.
Rhinitis (No, %)40 (68)26 (63)N.S.
Stage 1 Gina treatment (No, %)12 (20)8 (19)N.S.
Stage 2 Gina treatment (No, %)22 (37)15 (37)N.S.
Stage 3 Gina treatment (No, %)25 (43)18 (44)N.S.
Data are presented as median and IQ range unless noted otherwise, separately for gender. None of the differences was significant between male (M) and female (F) subgroups, (Mann–Whitney U-test, χ2 test) except for Age at enrolment.
Table
Table 2. Overall FEV1 rate of decline compared with other studies. FEV1 decline values were separately calculated for a male and a female.
Table 2. Overall FEV1 rate of decline compared with other studies. FEV1 decline values were separately calculated for a male and a female.
ReferenceAsthmaCOPD
MF
Quanjer (Bull Eur Physiopath Respir 1983)29 mL/year25 mL/year
Lange N Engl J Med 1998 38 mL/year
Peat Eur J Respir Dis 1987 50.5 mL/year
Fletcher 1976 (libro) 22 mL/year
Cuttitta Chest 2002 4041.3 mL/year
Burrows 1986 65 mL/year70 mL/year
Mannino Soriano (Am J Respir Crit Care Med 2009)18 mL/year
Kalhan R (Am J Med 2010) Framingham19.617.6 mL/year
O’ Byrne PM (Am J Respir Crit care Med 2009)27–34 mL/year
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Bucchieri, S.; Alfano, P.; Audino, P.; Cibella, F.; Fazio, G.; Marcantonio, S.; Cuttitta, G. Lung Function Decline in Adult Asthmatics—A 10-Year Follow-Up Retrospective and Prospective Study. Diagnostics 2021, 11, 1637. https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11091637

AMA Style

Bucchieri S, Alfano P, Audino P, Cibella F, Fazio G, Marcantonio S, Cuttitta G. Lung Function Decline in Adult Asthmatics—A 10-Year Follow-Up Retrospective and Prospective Study. Diagnostics. 2021; 11(9):1637. https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11091637

Chicago/Turabian Style

Bucchieri, Salvatore, Pietro Alfano, Palma Audino, Fabio Cibella, Giovanni Fazio, Salvatore Marcantonio, and Giuseppina Cuttitta. 2021. "Lung Function Decline in Adult Asthmatics—A 10-Year Follow-Up Retrospective and Prospective Study" Diagnostics 11, no. 9: 1637. https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11091637

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop