Underdiagnosis of Obstructive Lung Disease

Findings From the French CONSTANCES Cohort

Marie-Christine Delmas; Laetitia Bénézet; Céline Ribet; Yuriko Iwatsubo; Marie Zins; Rachel Nadif; Nicolas Roche; Bénédicte Leynaert

Disclosures

BMC Pulm Med. 2021;21(319)

Conclusion

The underdiagnosis of OLD is very common among adults in France. Many remain undiagnosed despite the significant burden of respiratory symptoms. Underdiagnosis affects not only people with mild airflow limitation but also those with more severe disease. This study highlights the need to reduce the underdiagnosis of OLD in the French population. Efforts should be made to raise awareness about OLD and respiratory symptoms in the general population through national campaigns using various media. Promoting the use of spirometry among primary care professionals along with more systematic screening for symptoms using structured questionnaires should also improve OLD diagnosis.

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Abbreviations
ATS: American Thoracic Society; COPD: Chronic obstructive pulmonary disease; ERS: European Respiratory Society; HPC: Health prevention centres; FEV₁: Forced expiratory volume in 1 s; FVC: Forced vital capacity; GLI: Global Lung Function Initiative; GOLD: Global Initiative on Obstructive Lung Disease; OLD: Obstructive lung disease.

Acknowledgements
The authors thank the team of the "Population-based Epidemiologic Cohorts Unit" (Cohortes epidemiologiques en population) that designed and manages the Constances Cohort Study. They also thank the French National Health Insurance Fund ("Caisse nationale d'assurance maladie", CNAM) and its Health Prevention Centres ("centres d'examens de sante"), which are collecting a large part of the data, the French Old-Age Insurance Fund ("Caisse nationale d'assurance vieillesse") for its contribution to the constitution of the cohort, and ClinSearch, Aqualab and EuroCell, which are conducting the data quality control. The authors also acknowledge the Constances Respiratory Group: MC Delmas, O Dumas, V Giraud, Y Iwatsubo, B Leynaert, N Le Moual, R Nadif, T Perez, N Roche, R Varraso.

Funding
The Constances Cohort Study was supported and funded by the French National Health Insurance Fund ("Caisse nationale d'assurance maladie", CNAM). The Constances Cohort Study is an "Infrastructure nationale en biologie et sante" and benefits from a grant from the French National Agency for Research (ANR-11-INBS-002). Constances is also partly funded by Merck Sharp & Dohme (MSD), AstraZeneca, Lundbeck and L'Oreal. None of these funding sources had any role in the design of the study, collection and analysis of data or decision to publish.

Availability of data and materials
Access to sensitive and personal data, such as those of the CONSTANCES cohort, is restricted by French law. The CONSTANCES coordination team makes the data available, upon request, to qualified researchers who have obtained prior authorization from the French national data protection authority (Commission nationale de l'informatique et des libertes, CNIL). Information for applicants to CONSTANCES data is available on the website: https://www.constances.fr/CFP.pdf. CONSTANCES investigators may be contacted at the following address: contact@constances.fr.

Declarations
Ethics approval and consent to participate
The authors assert that all procedures contributing to this work comply with the ethical standards of the national and institutional committees on human experimentation and with the Helsinki Declaration, as revised in 2008. All procedures were approved by the Institutional Review Board of the French Institute of Health Research (INSERM). The CONSTANCES cohort was also approved by the French Data Protection Agency (CNIL). All participants provided written informed consent.

Consent for publication
Not applicable.

Table 1. Characteristics of the study populationparticipants with airflow limitation
	All (N = 765)	Men (N = 385)	Women (N = 380)	P
Gender, %
Men	54.7
Women	45.3
Age (years), m	44.4	46.5	41.9	0.002
ISCED education level, %
0–2 (≤ lower secondary)	14.1	16.9	10.7	0.21
3–4 (upper secondary)	39.5	41.2	37.4
5–6 (short-cycle tertiary/bachelor)	30.0	27.0	33.5
7–8 (master/doctorate)	16.5	14.9	18.4
Tobacco status, %
Never	31.8	28.9	38.7	0.01
Ever < 10 pack-years	29.5	26.1	33.7
Ever ≥ 10 pack-years	37.3	45.0	27.5
Pack-years in smokers, m	18.4	22.9	11.8	< 0.001
BMI (kg/m²), m	25.0	25.4	24.5	0.17
Respiratory symptoms, %
Past-year wheezing	40.3	44.8	34.9	0.08
Chronic cough	17.0	18.8	15.0	0.38
Chronic sputum	12.5	15.1	9.4	0.16
Dyspnoea ≥ grade 2	19.9	16.1	24.6	0.07
≥ 1 symptom	51.9	52.9	50.7	0.69
OLD history, %
Asthma	29.6	26.0	33.9	0.11
COPD/Emphysema/Chronic bronchitis	8.1	11.4	4.1	0.02
Bronchiectasis	0.1	0.1	0.1	–
≥ 1 OLD	35.6	35.9	35.3	0.91
Cardiovascular history, %
IHD, stroke, PAD	3.4	5.5	1.0	0.03
Other	11.6	11.8	11.3
Lung function
FEV₁% predicted, m	75.3	72.5	76.4	< 0.001
FVC% predicted, m	92.9	90.4	93.2	0.003
FEV₁/FVC% predicted	80.5	79.7	80.8	0.003
GOLD severity, %
Mild	39.2	35.3	44.0	0.01
Moderate	53.5	53.4	53.6
Severe	7.3	11.2	2.5

BMI body mass index; COPD chronic obstructive pulmonary disease; FEV₁ forced expiratory volume in 1 s; FVC forced vital capacity; GOLD Global Initiative on Obstructive Lung Disease; IHD ischemic heart disease; ISCED International Standard Classification of Education; OLD obstructive lung disease; PAD peripheral arterial disease; P P value for the comparison of men and women
Data are presented as weighted percentage (%) or mean (m)
Missing values in 95 participants (10 for education level, 90 for tobacco status, 5 for BMI, 2 for respiratory symptoms)

Table 2. Comparison of people individuals with diagnosed and undiagnosed obstructive lung disease among thoseparticipants with airflow limitation
	Previous OLD diagnosis^a			P
	Asthma (N = 224)	COPD (N = 46)	No (N = 493)	P
Sociodemographic
Males, %	48.8	77.1	54.5	0.04
Age (years), m	41.8	58.5	43.8	< 0.001
ISCED education level, %
0–2 (≤ lower secondary)	9.3	37.6	13.4	0.004
3–4 (upper secondary)	36.3	42.1	40.4
≥ 5 (tertiary)	54.4	20.2	46.2
Tobacco consumption, %
Never	43.5	17.5	30.8	< 0.001
Ever < 10 pack-years	37.9	4.7	28.5
Ever ≥ 10 pack-years	18.6	77.8	40.7
BMI (kg/m²), m	24.6	27.4	24.8	0.38
Respiratory symptoms, %
Past-year wheezing	64.4	73.8	26.3	< 0.001
Chronic cough	14.8	33.4	16.1	0.10
Chronic sputum	11.8	22.9	11.5	0.29
Dyspnoea grade ≥ 2	20.9	51.8	15.6	< 0.001
≥ 1 symptom	72.6	79.7	39.7	< 0.001
Cardiovascular comorbidities, %
No	86.7	61.7	87.1	0.003
IHD, stroke, PAD	1.9	6.7	3.7
Other	11.4	31.8	9.2
Lung function
FEV₁ (L), m	2.56	1.80	2.75	< 0.001
FEV₁% predicted, m	72.8	58.0	78.5
GOLD severity, %				< 0.001
Mild	28.3	3.3	48.4
Moderate	64.9	56.3	48.4
Severe	6.8	40.4	3.3	< 0.001

BMI body mass index; COPD chronic obstructive pulmonary disease; FEV₁ forced expiratory volume in 1 s; GOLD Global Initiative on Obstructive Lung Disease; IHD ischemic heart disease; ISCED International Standard Classification of Education; OLD obstructive lung disease; PAD peripheral arterial disease
^aPrevious OLD diagnosis reported by the participants; Asthma: diagnosis of asthma only; COPD: diagnosis of COPD, emphysema, or chronic bronchitis associated with a diagnosis of asthma in eight patients; No: no diagnosis of OLD (asthma, COPD, emphysema, chronic bronchitis, or bronchiectasis)
Data are presented as weighted percentage (%) or weighted mean (m)
Missing values in 95 participants (10 for education level, 90 for tobacco status, 5 for BMI, 2 for respiratory symptoms)

Table 3. Respiratory symptoms according to the severity of airflow limitation in participants with and without a previous diagnosis of OLD
	GOLD severity			Total (N = 763)
	Mild N = 319	Moderate N = 4035	Severe N = 41	Total (N = 763)
No previous OLD diagnosis
Past-year wheezing, %	19.8	29.4	76.2	26.3
Chronic cough, %	10.1	21.1	28.0	16.1
Chronic sputum, %	6.4	16.4	14.6	11.5
Dyspnoea grade ≥ 2, %	9.1	20.1	44.4	15.6
≥ 1 symptom, %	28.8	47.6	84.1	39.7
Previous OLD diagnosis
Past-year wheezing, %	58.2	66.3	80.4	66.4
Chronic cough, %	21.3	15.3	30.8	18.9
Chronic sputum, %	13.1	12.2	25.2	14.4
Dyspnoea grade ≥ 2, %	25.2	21.6	57.6	27.8
≥ 1 symptom, %	71.2	73.7	80.9	74.2
Total
Past-year wheezing, %	27.6	44.6	79.1	40.3
Chronic cough, %	12.4	18.7	29.9	17.0
Chronic sputum, %	7.8	14.7	22.1	12.5
Dyspnoea grade ≥ 2, %	12.4	20.7	53.7	19.9
≥ 1 symptom, %	37.6	58.4	81.8	51.9

COPD chronic obstructive pulmonary disease; GOLD Global Initiative on Obstructive Lung Disease; OLD obstructive lung disease
Data are presented as weighted percentage (%)

Table 4. Factors associated with undiagnosed obstructive lung disease (OLD), multivariate analyses in participants with airflow limitation
	aPR (95% CI)
	Model 1		Model 2
Gender
Men	1		1
Women	1.12	(0.96–1.30)	1.05	(0.90–1.23)
Age
For 10-year increase	0.96	(0.89–1.02)	0.98	(0.92–1.05)
ISCED education level
≤ 4 (≤ upper secondary)	1		1
≥ 5 (tertiary)	0.92	(0.78–1.08)	0.93	(0.79–1.15)
Tobacco consumption
Never	1		1
Ever < 10 pack-years	0.97	(0.79–1.19)	0.95	(0.78–1.14)
Ever ≥ 10 pack-years	1.36	(1.11–1.67)	1.35	(1.11–1.64)
Respiratory symptoms
≥ 1	1		1
No	1.67	(1.42–1.97)	1.51	(1.28–1.78)
Cardiovascular comorbidities
No	1		1
Yes	0.95	(0.74–1.22)	1.01	(0.79–1.28)
FEV₁% predicted
For 10-point increase			1.12	(1.06–1.19)

aPR adjusted prevalence ratio; CI confidence interval; FEV₁ forced expiratory volume in 1 s; ISCED International Standard Classification of Education
Weighted robust Poisson regression models adjusted for gender, age, education, tobacco consumption, respiratory symptoms and cardiovascular comorbidities (model 1), plus FEV1 (model 2) in 670 participants with complete data on covariates