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)

Abstract and Introduction

Abstract

Background: The burden of undiagnosed obstructive lung disease (OLD) (mainly asthma and chronic obstructive pulmonary disease) is not fully established, and targets for corrective action are yet to be identified. We assessed the underdiagnosis of OLD and its determinants in France.

Methods: CONSTANCES is a French population-based cohort of adults aged 18–69 years at inception. We analysed data collected at inclusion in 2013–2014. Undiagnosed OLD was defined as spirometry-confirmed airflow limitation (FEV₁/FVC < lower limit of normal) without prior diagnosis of asthma, chronic obstructive pulmonary disease, or bronchiectasis. Multivariate analysis was performed with weighted robust Poisson regression models to estimate the adjusted prevalence ratios (aPR) of undiagnosed OLD.

Results: Spirometry results were available for 19,398 participants. The prevalence of airflow limitation was 4.6%. Overall, 64.4% of adults with airflow limitation did not report a previous diagnosis of OLD. Individuals with high cumulative tobacco consumption (≥ 10 pack-years) (aPR: 1.72 [1.28–2.32]), without respiratory symptoms (aPR: 1.51 [1.28–1.78]), and with preserved lung function (aPR: 1.21 [1.04–1.41] for a 10-point increase in FEV₁% predicted) had a higher risk of being undiagnosed. Half of symptomatic individuals with airflow limitation (45% of those with moderate to severe airflow limitation) were undiagnosed with OLD.

Conclusion: Underdiagnosis of OLD is very common among French adults, even in patients with respiratory symptoms. Efforts should be made in France to raise awareness about OLD in the general population, improve the detection of respiratory symptoms, and increase the use of spirometry among primary care professionals.

Introduction

Obstructive lung disease (OLD), which mainly relates to asthma and chronic obstructive pulmonary disease (COPD), is both common and serious, representing a growing public health challenge worldwide.^[1] Nevertheless, asthma and COPD are frequently undiagnosed. Regarding asthma, population-based studies showed that 20% to 70% of adults with current asthma remained undiagnosed.^[2] A pooled analysis of national and international COPD surveys estimated that 81% of COPD patients were undiagnosed.^[3] In France, the most recent estimate of the prevalence of current asthma in adults varies from 6 to 9% according to the definition.^[4] In the early 2000s, the prevalence of airflow limitation (based on pre-bronchodilator tests) was estimated at 7.5% among non-asthmatic individuals aged 45 years and over.^[5] A recent study conducted in middle-aged adults living in two northern French cities showed prevalence estimates ranging from 9.5% to 16.0% according to the city and definition used.^[6] More than 70% of those with airflow limitation did not report a diagnosis of OLD.

Undiagnosed OLD is associated with negative health outcomes such as respiratory symptoms, functional impairment and exacerbation, treatment delays, and substantial healthcare utilisation.^[7–9] Identifying the factors that contribute to undiagnosed OLD is therefore essential. The present analysis aimed to estimate the prevalence of undiagnosed OLD and identify the risk factors for underdiagnosis in the large French population-based CONSTANCES cohort.

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Next Section

Abstract and Introduction
Methods
Results
Discussion
Conclusion
References

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