Lung function decline in asthma patients with elevated bronchial CD8, CD4 and CD3 cells

Which inflammatory markers in the bronchial mucosa of asthma patients are associated with decline of lung function during 14 years of prospective follow-up?To address this question, 19 mild-to-moderate, atopic asthmatic patients underwent spirometry and bronchoscopy at baseline and after 14 years of follow-up (t=14). Baseline bronchial biopsies were analysed for reticular layer thickness, eosinophil cationic protein (EG2), mast cell tryptase (AA1), CD3, CD4 and CD8. Follow-up biopsies were stained for EG2, AA1, neutrophil elastase, CD3, CD4, CD8, CD20, granzyme B, CD68, DC-SIGN, Ki67 and mucins.Decline in forced expiratory volume in 1 s (FEV1) % predicted was highest in patients with high CD8 (p=0.01, both pre- and post-bronchodilator) or high CD4 counts at baseline (p=0.04 pre-bronchodilator, p=0.03 post-bronchodilator). Patients with high CD8, CD3 or granzyme B counts at t=14 also exhibited faster decline in FEV1 (p=0.00 CD8 pre-bronchodilator, p=0.04 CD8 post-bronchodilator, p=0.01 granzyme B pre-bronchodilator, and p<0.01 CD3 pre-bronchodilator).Long-term lung function decline in asthma is associated with elevation of bronchial CD8 and CD4 at baseline, and CD8, CD3 and granzyme B at follow-up. This suggests that high-risk groups can be identified on the basis of inflammatory phenotypes.

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The effect of smoking on lung function: a clinical study of adult-onset asthma

European Respiratory Journal ◽

10.1183/13993003.00850-2016 ◽

2016 ◽

Vol 48 (5) ◽

pp. 1298-1306 ◽

Cited By ~ 32

Author(s):

Minna Tommola ◽

Pinja Ilmarinen ◽

Leena E. Tuomisto ◽

Jussi Haanpää ◽

Terhi Kankaanranta ◽

...

Keyword(s):

Lung Function ◽

Multivariate Regression Analysis ◽

Forced Expiratory Volume ◽

Smoking History ◽

Adult Onset ◽

Lung Function Decline ◽

Adult Asthma ◽

Asthma Patients ◽

Annual Decline

The aim of this study was to evaluate the effect of smoking on lung function decline in adult-onset asthma in a clinical, 12-year follow-up study.In the Seinäjoki Adult Asthma Study, 203 patients were followed for 12 years (1999–2013) after diagnosis of new-onset adult asthma. Patients were divided into two groups based on smoking history: <10 or ≥10 pack-years. Spirometry evaluation points were: 1) baseline, 2) the maximum lung function during the first 2.5 years after diagnosis (Max0–2.5) and 3) after 12 years of follow-up.Between Max0–2.5 and follow-up, the median annual decline in absolute forced expiratory volume in 1 s (FEV1) was 36 mL in the group of patients with <10 pack-years of smoking and 54 mL in those with smoking history ≥10 pack-years (p=0.003). The annual declines in FEV1 % pred (p=0.006), forced vital capacity (FVC) (p=0.035) and FEV1/FVC (p=0.045) were also accelerated in the group of patients with ≥10 pack-years smoked. In multivariate regression analysis, smoking history ≥10 pack-years became a significant predictor of accelerated decline in FEV1.Among patients with clinically defined adult-onset asthma, smoking history ≥10 pack-years is associated with accelerated loss of lung function.

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Lung function, forced expiratory volume in 1 s decline and COPD hospitalisations over 44 years of follow-up

European Respiratory Journal ◽

10.1183/13993003.01575-2015 ◽

2015 ◽

Vol 47 (3) ◽

pp. 742-750 ◽

Cited By ~ 8

Author(s):

Suneela Zaigham ◽

Per Wollmer ◽

Gunnar Engström

Keyword(s):

Lung Function ◽

Airflow Obstruction ◽

Fixed Ratio ◽

Population Based ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Lung Function Decline ◽

Obstructive Pulmonary Disease ◽

Hazard Ratios

The use of baseline lung function in the prediction of chronic obstructive pulmonary disease (COPD) hospitalisations, all-cause mortality and lung function decline was assessed in the population-based “Men Born in 1914” cohort.Spirometry was assessed at age 55 years in 689 subjects, of whom 392 had spirometry reassessed at age 68 years. The cohort was divided into three groups using fixed ratio (FR) and lower limit of normal (LLN) criterion: forced expiratory volume in 1 s (FEV1)/vital capacity (VC) ≥70%, FEV1/VC <70% but ≥LLN (FR+LLN−), and FEV1/VC <70% and <LLN (FR+LLN+).Over 44 years of follow-up, 88 men were hospitalised due to COPD and 686 died. Hazard ratios (95% CI) for incident COPD hospitalisation were 4.15 (2.24–7.69) for FR+LLN− and 7.88 (4.82–12.87) for FR+LLN+ (reference FEV1/VC ≥70%). Hazard ratios for death were 1.30 (0.98–1.72) for FR+LLN− and 1.58 (1.25–2.00) for FR+LLN+. The adjusted FEV1 decline between 55 and 68 years of age was higher for FR+LLN− and FR+LLN+ relative to the reference. Of those with FR+LLN− at 55 years, 53% had progressed to the FR+LLN+ group at 68 years.Airflow obstruction at age 55 years is a powerful risk factor for future COPD hospitalisations. The FR+LLN− group should be carefully evaluated in clinical practice in relation to future risks and potential benefit from early intervention. This is reinforced by the increased FEV1 decline in this group.

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Serum Eosinophilic cationic protein (ECP) as an effective biological marker to monitor therapy in bronchial asthma patients.

Bangladesh Journal of Medical Microbiology ◽

10.3329/bjmm.v5i1.15813 ◽

2011 ◽

Vol 5 (1) ◽

pp. 3-7 ◽

Cited By ~ 1

Author(s):

Afroza Begum ◽

Humayun Sattar ◽

Abu Naser Ibne Sattar ◽

Md. Ruhul Amin Miah ◽

Ahmed Abu Saleh

Keyword(s):

Bronchial Asthma ◽

Persistent Asthma ◽

Biological Marker ◽

Forced Expiratory Volume ◽

Asthma Therapy ◽

Eosinophilic Cationic Protein ◽

Cationic Protein ◽

Before And After ◽

Asthma Patients

Clinically diagnosed bronchial asthma patients comprising of new cases, on therapy or follow up were enrolled for this study to see if the new biological marker Eosinophilic cationic protein (ECP) can be used as a more precise marker to monitor therapy than the presently used conventional ones like FEV1% predicted, PEFR, and Circulating eosinophil (C.E) count. Out of 70 bronchial asthma patients, 30 intermittent, 4 mild persistent, 24 moderate persistent and 12 severe persistent asthma patients were included, while 45 cases were enrolled for follow up. Serum level of eosinophil granular protein, Eosinophilic cationic protein (ECP) was measured in relation to changes in their forced expiratory volume in 1st second (FEV1% predicted) and Circulating Eosinophil count (%) before and after therapy in 45 follow up patients on asthma therapy. In this study, it was observed that C.E count (%) and FEV1% predicted were not decreased significantly and serum eosinophilic cationic protein (ECP) decreased significantly (p<0.001) after asthma therapy. Thus, serum ECP level can be used as a biological marker than other conventionally used marker (FEV1, C.E count) to monitor therapeutic efficacy in bronchial asthma patients.DOI: http://dx.doi.org/10.3329/bjmm.v5i1.15813 Bangladesh J Med Microbiol 2011; 05 (01): 3-7

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Trajectory and mortality of preserved ratio impaired spirometry: the Rotterdam Study

European Respiratory Journal ◽

10.1183/13993003.01217-2019 ◽

2019 ◽

Vol 55 (1) ◽

pp. 1901217 ◽

Cited By ~ 9

Author(s):

Sara Renata Alex Wijnant ◽

Emmely De Roos ◽

Maryam Kavousi ◽

Bruno Hugo Stricker ◽

Natalie Terzikhan ◽

...

Keyword(s):

Lung Function ◽

Chronic Obstructive Lung Disease ◽

Population Based ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Rotterdam Study ◽

Lung Function Decline ◽

Cardiovascular Comorbidities ◽

Age Related

Preserved ratio impaired spirometry (PRISm) is a heterogeneous condition but its course and disease progression remain to be elucidated. We aimed to examine its prevalence, trajectories and prognosis in the general population.In the Rotterdam Study (population-based prospective cohort) we examined prevalence, trajectories and prognosis of subjects with normal spirometry (controls; forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.7, FEV1 ≥80%), PRISm (FEV1/FVC ≥0.7, FEV1 <80%) and chronic obstructive pulmonary disease (COPD) (FEV1/FVC <0.7) at two study visits. Hazard ratios with 95% confidence intervals for mortality (until December 30, 2018) were adjusted for age, sex, body mass index, current smoking and pack-years.Of 5487 subjects (age 69.1±8.9 years; 7.1% PRISm), 1603 were re-examined after 4.5 years. Of the re-examined PRISm subjects, 15.7% transitioned to normal spirometry and 49.4% to COPD. Median lung function decline was highest in subjects with incident PRISm (FEV1 −92.8 mL·year−1, interquartile range (IQR) −131.9– −65.8 mL·year−1; FVC −93.3 mL·year−1, IQR −159.8– −49.1 mL·year−1), but similar in persistent PRISm (FEV1 −30.2 mL·year−1, IQR −67.9– −7.5 mL·year−1; FVC −20.1 mL·year−1, IQR −47.7–21.7 mL·year−1) and persistent controls (FEV1 −39.6 mL·year−1, IQR −64.3–−12.7 mL·year−1; FVC −20.0 mL·year−1, IQR −55.4–18.8 mL·year−1). Of 5459 subjects with informed consent for follow-up, 692 (12.7%) died during 9.3 years (maximum) follow-up: 10.3% of controls, 18.7% of PRISm subjects and 20.8% of COPD subjects. Relative to controls, subjects with PRISm and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2–4 had increased all-cause mortality (PRISm: HR 1.6, 95% CI 1.2–2.0; COPD GOLD 2–4: HR 1.7, 95% CI 1.4–2.1) and cardiovascular mortality (PRISm: HR 2.8, 95% CI 1.5–5.1; COPD 2–4: HR 2.1, 95% CI 1.2–3.6). Mortality within <1 year was highest in PRISm, with patients often having cardiovascular comorbidities (heart failure or coronary heart disease; 70.0%).PRISm is associated with increased mortality and this population encompasses at least three distinct subsets: one that develops COPD during follow-up, a second with high cardiovascular burden and early mortality, and a third with persistent PRISm and normal age-related lung function decline.

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The CRP genotype, serum levels and lung function in men: the Caerphilly Prospective Study

Clinical Science ◽

10.1042/cs20100504 ◽

2010 ◽

Vol 120 (8) ◽

pp. 347-355 ◽

Cited By ~ 23

Author(s):

Charlotte E. Bolton ◽

Wiebke Schumacher ◽

John R. Cockcroft ◽

Nicholas J. Timpson ◽

George Davey Smith ◽

...

Keyword(s):

Lung Function ◽

Prospective Study ◽

Causal Effect ◽

Serum Levels ◽

Forced Expiratory Volume ◽

Reverse Causality ◽

Lung Function Decline ◽

Impaired Lung Function ◽

Serum Crp

Systemic CRP (C-reactive protein) has been associated with impaired lung function. A causal relationship would increase the value of CRP as both a diagnostic and therapeutic tool. We assessed the association between lung function parameters, circulating CRP and CRP polymorphisms using Mendelian randomization in efforts to attribute causality to known associations. Spirometric parameters of FEV1 (forced expiratory volume in 1 s) and FVC (forced vital capacity) were determined in 2173 men participating in the Caerphilly Prospective Study. Lung function measures on 1021 participants were available at follow-up (mean, 16.8 years later). Serum CRP levels were measured at baseline, and three CRP polymorphisms were analysed. Haplotype analysis was performed. Serum CRP levels at baseline were inversely associated with contemporaneous FEV1 and FVC as well as at follow-up (P<0.001) even after adjustment for conventional confounders. Serum CRP was associated with FEV1 decline (P=0.04). All three CRP polymorphisms (rs1800947, rs1130864 and rs1205) predicted serum CRP; however, there were no clear associations of the polymorphisms or haplotypes with lung function or with lung function decline. In conclusion, serum CRP was associated with lung function cross-sectionally; however, CRP polymorphisms were not associated with lung function or decline, suggesting that the CRP–lung function relationship is due to reverse causality, an unmeasured confounding factor or only has a modest causal effect.

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Serum 25-hydroxyvitamin D level, smoking and lung function in adults: the HUNT Study

European Respiratory Journal ◽

10.1183/09031936.00226614 ◽

2015 ◽

Vol 46 (2) ◽

pp. 355-363 ◽

Cited By ~ 7

Author(s):

Tricia L. Larose ◽

Ben M. Brumpton ◽

Arnulf Langhammer ◽

Carlos A. Camargo ◽

Yue Chen ◽

...

Keyword(s):

Lung Function ◽

Forced Expiratory Volume ◽

Lung Function Decline ◽

Cross Sectional ◽

Hydroxyvitamin D ◽

Impaired Lung Function ◽

25 Hydroxyvitamin D ◽

Hunt Study ◽

Never Smokers

The association between serum 25-hydroxyvitamin D (25(OH)D) level and lung function changes in the general population remains unclear.We conducted cross-sectional (n=1220) and follow-up (n=869) studies to investigate the interrelationship of serum 25(OH)D, smoking and lung function changes in a random sample of adults from the Nord-Trøndelag Health (HUNT) Study, Norway.Lung function was measured using spirometry and included forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % pred and FEV1/FVC ratio. Multiple linear and logistic regression models estimated the adjusted difference in lung function measures or lung function decline, adjusted odds ratios for impaired lung function or development of impaired lung function and 95% confidence intervals.40% of adults had serum 25(OH)D levels <50 nmol·L−1. Overall, those with a serum 25(OH)D level <50 nmol·L−1 showed worse lung function and increased odds of impaired lung function compared to the ≥50 nmol·L−1 group. These associations tended to be stronger among ever-smokers, including greater decline in FEV1/FVC ratio and greater odds of the development of impaired lung function (FEV1/FVC <70% OR 2.4, 95% CI 1.2–4.9). Associations among never-smokers were null. Results from cross-sectional and follow-up studies were consistent. There were no associations between serum 25(OH)D levels and lung function or lung function changes in never-smokers, whereas significant associations were observed in ever-smokers.

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Pulmonary exacerbations as a risk factor for lung function decline-experiences of the National Cystic Fibrosis Center

Vojnosanitetski pregled ◽

10.2298/vsp171114005g ◽

2019 ◽

Vol 76 (11) ◽

pp. 1110-1114

Author(s):

Bojana Gojsina ◽

Milan Rodic ◽

Jelena Visekruna ◽

Goran Trajkovic ◽

Aleksandar Sovtic ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Burkholderia Cepacia ◽

Negative Impact ◽

Bacterial Colonization ◽

Forced Expiratory Volume ◽

Lung Function Decline ◽

Pulmonary Exacerbations ◽

Fev1 Decline

Background/Aim. Pulmonary exacerbations have negative impact on clinical course of cystic fibrosis (CF) lung disease being associated with a steeper decline in the lung function, unfavorable prognosis and impaired quality of life. The aim of this study was to determine whether an increased number of exacerbations had influence on the lung function in the patients with CF, as well as to estimate the nutritional status, gender, presence of comorbid conditions and bacterial colonization of airways as predictive factors for pulmonary exacerbations. Methods. This retrospective cohort study included 83 pediatric and adult patients, treated from 2011? 2015 in the Mother and Child Health Institute of Serbia ?Dr Vukan Cupic?. The best result of forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) in each year of follow-up was taken into account to calculate the five-year trend values of these indicators. The number of exacerbations per year of follow-up and its impact on the FEV1 decline was evaluated. Results. Mean annual decline of FEV1 and FVC were 2.4% and 1.7% respectively. The malnourished patients had the lower initial values of FEV1 and FVC, and more frequent exacerbations in comparison with the normal weight and overweight patients. The frequency of exacerbations was significantly higher in the patients chronically colonized with Burkholderia cepacia (p = 0.023). The increased number of exacerbation was proved to be the most important factor in a prediction of FEV1 decline over time (p = 0.013). Conclusion. Pulmonary exacerbations lead to the more progressive lung function decline in the patients with CF. Malnourishment and chronic airway colonization with Burkholderia cepacia result in more frequent pulmonary exacerbations.

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

Diagnostics ◽

10.3390/diagnostics11091637 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1637

Author(s):

Salvatore Bucchieri ◽

Pietro Alfano ◽

Palma Audino ◽

Fabio Cibella ◽

Giovanni Fazio ◽

...

Keyword(s):

Lung Function ◽

Prospective Study ◽

Forced Expiratory Volume ◽

Lung Function Decline ◽

Factors Affecting ◽

Adult Asthmatic ◽

Higher Doses ◽

Fev1 Decline ◽

Over Time

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.

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Air Trapping Is Associated with Heterozygosity for Alpha-1 Antitrypsin Mutations in Patients with Asthma

Respiration ◽

10.1159/000513072 ◽

2021 ◽

pp. 1-10

Author(s):

Marina Aiello ◽

Marianna Ghirardini ◽

Laura Marchi ◽

Annalisa Frizzelli ◽

Roberta Pisi ◽

...

Keyword(s):

Lung Function ◽

Serum Concentration ◽

Forced Expiratory Volume ◽

Small Airway ◽

University Hospital ◽

Air Trapping ◽

Asthmatic Patients ◽

Alpha 1 Antitrypsin Deficiency ◽

Alpha 1 Antitrypsin ◽

Few Data

Background: Alpha-1 antitrypsin deficiency (AATD) is a hereditary disorder involving lungs, characterized by low serum concentration of the protein alpha-1 antitrypsin (AAT) also called proteinase inhibitor (PI). Asthma is common in AATD patients, but there are only few data on respiratory function in asthmatic patients with AATD. Objectives: The aim of the study was to evaluate lung function in asthmatic outpatients with mutation in the SERPINA1 gene coding for AAT versus asthmatic subjects without mutation. Methods: We performed the quantitative analysis of the serum concentration of AAT in 600 outpatients affected by mild to moderate asthma from the University Hospital of Parma, Italy. Fifty-seven of them underwent the genetic analysis subsequently; they were subdivided into mutated and non-mutated subjects. All the mutated patients had a heterozygous genotype, except 1 (PI*SS). We assessed the lung function through a flow-sensing spirometer and the small airway parameters through an impulse oscillometry system. Results: The values of forced vital capacity (% predicted) and those of the residual volume to total lung capacity ratio (%) were, respectively, lower and higher in patients mutated versus patients without mutation, showing a significantly greater air trapping (p = 0.014 and p = 0.017, respectively). Moreover, patients with mutation in comparison to patients without mutation showed lower forced expiratory volume in 3 s (% predicted) and forced expiratory volume in 6 s (L) spirometric values, reflecting a smaller airways contribution. Conclusions: In asthmatic patients, heterozygosity for AAT with PI*MZ and PI*MS genotypes was associated with small airway dysfunction and with lung air trapping.

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Lung function decline is associated with serum uric acid in Korean health screening individuals

Scientific Reports ◽

10.1038/s41598-021-89678-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kyung-Min Ahn ◽

Suh-Young Lee ◽

So-Hee Lee ◽

Sun-Sin Kim ◽

Heung-Woo Park

Keyword(s):

Uric Acid ◽

Lung Function ◽

Serum Uric Acid ◽

Uric Acid Level ◽

Acid Level ◽

Serum Uric Acid Level ◽

Forced Expiratory Volume ◽

Linear Regression Models ◽

Lung Function Decline ◽

Health Screenings

AbstractWe performed a retrospective cohort study of 19,237 individuals who underwent at least three health screenings with follow-up periods of over 5 years to find a routinely checked serum marker that predicts lung function decline. Using linear regression models to analyze associations between the rate of decline in the forced expiratory volume in 1 s (FEV1) and the level of 10 serum markers (calcium, phosphorus, uric acid, total cholesterol, total protein, total bilirubin, alkaline phosphatase, aspartate aminotransferase, creatinine, and C-reactive protein) measured at two different times (at the first and third health screenings), we found that an increased uric acid level was significantly associated with an accelerated FEV1 decline (P = 0.0014 and P = 0.037, respectively) and reduced FEV1 predicted % (P = 0.0074 and P = 8.64 × 10–7, respectively) at both visits only in non-smoking individuals. In addition, we confirmed that accelerated forced vital capacity (FVC) and FEV1/FVC ratio declines were observed in non-smoking individuals with increased serum uric acid levels using linear mixed models. The serum uric acid level thus potentially predicts an acceleration in lung function decline in a non-smoking general population.

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