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) 

In This Article

Discussion

This study highlights a high level of OLD underdiagnosis in France. Only 36% of adults with airflow limitation reported a previous diagnosis of OLD. High tobacco consumption, an absence of respiratory symptoms (wheezing, chronic cough or phlegm, dyspnoea), and preserved lung function were associated with a higher risk of being undiagnosed. However, nearly half (45%) of adults with moderate to severe airflow limitation (FEV1/FVC < LLN and FEV1 < 80% predicted) remained underdiagnosed with OLD despite experiencing respiratory symptoms.

The major strength of our study is the large sample of the French population, randomly drawn from the general population. We employed reweighting procedures using demographic, socioeconomic, clinical, and healthcare consumption data to correct for non-participation in the study. However, reweighting procedures did not fully correct for the selection bias of the study population. No participants in the CONSTANCES cohort had very severe airflow limitation, which tends to underestimate the prevalence of airflow limitation, and since such severe patients are likely to be diagnosed, to overestimate OLD underdiagnosis.

In our study, airflow limitation was defined based on pre-bronchodilator spirometry, which does not distinguish between asthma and COPD. To estimate the overall prevalence of undiagnosed OLD, pre-bronchodilator (ideally, both pre- and post-bronchodilator) spirometry is more relevant than only post-bronchodilator spirometry, which may miss asthmatic patients with fully reversible airflow limitation. However, lung function testing cannot estimate the rate of asthma underdiagnosis, since many patients, even untreated, can have normal spirometry. Further, pre-bronchodilator spirometry cannot be used to estimate the prevalence and underdiagnosis of COPD, since this diagnosis requires airflow limitation to persist after administering bronchodilators. Another limitation of our study is that diagnosed OLD was defined as a previous diagnosis of asthma, COPD, chronic bronchitis, emphysema, or bronchiectasis reported by participants with airflow limitation, without validating the diagnoses in their medical charts.

We estimated that 64% of French adults with OLD (as identified by pre-bronchodilator airflow limitation) were undiagnosed. Studies assessing OLD underdiagnosis based on pre-bronchodilator spirometry are relatively scarce. In the USA, the analysis of two nationally representative health examination surveys showed that more than 70% of adults aged 20–79 years with obstructive spirometry pattern (pre-bronchodilator FEV1/FVC < 0.70) were not diagnosed with asthma or COPD and that underdiagnosis did not change from the first study in 1988–1994 to the second in 2007–2012.[19] A large underdiagnosis of asthma has been evidenced in both children and adults, including the elderly, with underdiagnosis rates ranging from 20 to 70%.[2] The rate of COPD underdiagnosis appeared to be even higher. Using data from national or international surveys conducted in randomly selected adults aged ≥ 40 years, it was found that 50% to 98% of COPD cases (defined by a post-bronchodilator FEV1/FVC < LLN) were undiagnosed, with an average rate of 81%.[3] In France, a study conducted in the early 2000s estimated that 94% of non-asthmatics aged 40 years and over with airflow limitation (pre-bronchodilator FEV1/FVC < 0.70) had not been diagnosed with chronic respiratory disease.[5] In northern France in 2011–2013, 72% of middle-aged adults with pre-bronchodilator FEV1/FVC < LLN did not report a diagnosis of asthma or COPD.[6] Using the same definition for airflow limitation, we estimated a slightly lower rate (64% overall, and 62% among adults aged 40–69 years).

Several factors may explain the high underdiagnosis of OLD. First, respiratory symptoms may not be present. We found that 48% of individuals with airflow limitation did not report respiratory symptoms (including past-year wheezing, chronic cough or sputum, and dyspnoea grade ≥ 2), with this rate being still high (39%) among those with moderate to severe airflow limitation. However, 49% of individuals with airflow limitation remained underdiagnosed despite the presence of respiratory symptoms. The underreporting of respiratory symptoms to general practitioners by asthmatic patients was shown to contribute significantly to the underdiagnosis of asthma.[20] Regarding COPD, the general population's limited awareness about this disease and its consequences probably plays an important role in the underreporting of symptoms to general practitioners. In 2017, in France, only 22% of adults reported knowing about COPD, among whom only one-third cited tobacco use as the main cause.[21] Similar figures have been reported worldwide.[22–24] The poor recognition of respiratory symptoms suggestive of COPD by primary care professionals might also play a role. Another reason for the underdiagnosis of OLD is the low use of spirometry. In France, spirometry testing is mainly performed in hospital settings or pulmonologists' offices. As in many other countries, screening for COPD in the general population is not recommended, but early case finding of COPD is. According to clinical guidelines, spirometry tests should be performed in all patients aged 40 years and over with respiratory symptoms, along with cumulative tobacco exposure of ≥ 15 pack-years or occupational exposure to smoke, gas, or dust.[25] Several initiatives are currently being developed to expand spirometry testing to general practices to decrease the underdiagnosis of COPD, but the results are still pending.

In line with previous population-based studies on COPD underdiagnosis,[3,26] we found that OLD underdiagnosis was more frequent in adults with fewer symptoms and better lung function. COPD is often not recognised in patients with limited respiratory symptoms and preserved lung function, with the diagnosis being delayed until late in the disease process. Studies showed that 20–30% of patients admitted to emergency departments or hospitalised for the first time for COPD exacerbation had not been previously diagnosed or treated.[27–29]

We defined airflow limitation using pre-bronchodilator spirometry, which encompasses both persistent and reversible airflow limitation. To increase the specificity of pre-bronchodilator airflow limitation for COPD, we restricted the study population to participants with moderate to severe airflow limitation (FEV1 < 80% predicted). It was shown that the proportion of pre-bronchodilator airflow limitation that persists after administering bronchodilators was higher (above 85%) in adults with FEV1 < 80% predicted.[30] We also restricted the study population to participants aged 40 years and over, since COPD is extremely rare in young adults. These analyses yielded similar results to those observed for all participants with airflow limitation, with an increased risk of being undiagnosed in those without respiratory symptoms, with preserved lung function, and with a high cumulative tobacco consumption. By contrast, in participants aged under 40 years, no significant association with tobacco consumption was observed. These results could suggest that the association between tobacco consumption and OLD underdiagnosis is related to COPD underdiagnosis.

Despite having less severe airway obstruction and fewer comorbidities than those with a clinical diagnosis of asthma or COPD, people with undiagnosed OLD had a higher mortality risk than the general population.[19] Undiagnosed COPD patients often experience exacerbations, and compared to individuals without COPD, they have impaired health-related quality of life and increased healthcare use.[7,9,31,32] In the absence of diagnosis, these patients cannot be properly managed for their disease, although effective treatments are available to stop smoking, prevent respiratory infections, relieve symptoms, decrease exacerbation risk, and limit quality-of-life impairment.[12] Some treatments were recently shown to decrease mortality in some subpopulations.[33,34] Regarding asthma, evidence shows that early intervention, particularly with inhaled corticosteroids, has a substantial impact on quality of life and later morbidity.[35]

No data on time trends in asthma prevalence among French adults are available, but repeated prevalence surveys among children show an increasing trend.[36,37] Regarding COPD, increased hospital admissions for COPD exacerbation have been observed.[38] Due to the delay in the mass uptake of smoking in women in the twentieth century, between-gender discrepancies in the current trends for COPD burden are observed. Between 2002 and 2015, the rate of patients hospitalised for COPD exacerbation increased by 100% in women and 30% in men. COPD prevalence modelling in France predicted an increase in prevalence (for both diagnosed and undiagnosed COPD) between 2005 and 2015, especially in women.[39] If the underdiagnosis of OLD is not substantially reduced, the number of undiagnosed individuals will continue to increase in the coming years.

processing....