There is an urgent need to start diagnosing COPD, or at least identify risk, at a much earlier stage if we want to improve the outcomes of patients, delegates in a session on COPD at the 2019 ERS Congress in Madrid have heard.

In a Menarini-sponsored session – the ABCD of COPD – international expert Professor Alvar Agusti from the Respiratory Institute, Hospital Clinic and University of Barcelona in Spain, said the traditional COPD paradigm of a self-inflicted, smoking-induced disease leading to a rapid decline in lung function was outdated.¹

Instead there should be a much broader approach, which took into account the many other impacts on lung health trajectories throughout life.

These included maternal smoking, premature birth, infection, air pollution and occupational exposures.

Professor Agusti said respiratory physicians were familiar with historical lung function decline curves in COPD. But many of those curves only looked at people in their 60s to 70s or assumed everyone started with perfect lung function at age 25.

He told delegates that about 10% of the population does not develop normal lung function by early adulthood.

And those with lower than normal FEV₁ in early adulthood were more likely to develop not just respiratory disease but cardiovascular and metabolic disease about a decade earlier than people with normal lung function.²

This suggested COPD was the pulmonary component of systemic, multi-morbid syndrome and that earlier intervention had much to offer.

Professor Agusti said while the mean age of COPD diagnosis was in the mid-to-late 60s, there should be a concerted effort to define the earlier lung function trajectories that result in COPD.³

He said a clinical research collaboration, the Chronic Airway Diseases Early Stratification (CADSET), was underway.⁴

Three of the five working groups would focus on suboptimal lung development from conception to 25 years, clinical and biological biomarkers of lung function decline from 25 to 50 years, and multilevel data such as genetics, genomics, methylation and proteomics on biological samples from age 50 years.

But how early was too early to identify COPD risk? he asked.

Professor Agusti suggested teenagers could be screened at the time of receiving their driver’s license. Or even earlier as children aged 7-8 years were perfectly capable of performing spirometry.

And there was growing, disturbing evidence that even pre-conception exposures in parents could be passed on as risk to subsequent generations.

“To me the important issue is that there is pretty clear evidence that we have to move upstream and we have to diagnose early. Clearly we need to diagnose before the age at which we are doing it now.”

He said it was possible that some of the medications currently used in COPD, might be even more effective in earlier disease.

“A young individual is likely to have a better repair capacity than an old individual. So maybe if we intervene early the repair of the damaged lung might be better. But this is maybe. It needs to be explored. It’s a hypothesis.”

Speaking in the same session, Professor Bartolome Celli, from Harvard Medical School and director of the COPD Center at Brigham and Women’s Hospital in Boston, said COPD began well before any obstruction.

And he emphasised that early COPD was related to earlier age of onset and was not the same as mild COPD, which related to the severity of airflow limitation.

He told delegates that pre-COPD might become a legitimate label in the near future.

Certainly other medical disciplines had accepted and intervened in early disease for example in prehypertension, prediabetes, pre-eclampsia or precancerous lesions, he said.

Interventions in pre-COPD could include smoking cessation to help normalise lung function or vaccination against preventable respiratory infections.

Professor Celli said spirometry was a good biomarker for future COPD.

Low baseline lung function and rapid decline as measured via serial spirometry in a cohort of smokers 40-50 years of age had been shown to be associated with a odds ratio of 36.6 for developing COPD, compared to smokers with a high baseline lung function and no decline.⁵

The study defined rapid lung function decline as >40ml FEV₁ per year.

Professor Celli said these people could be defined as having pre-COPD with COPD diagnosis reserved for those with persistent airflow limitation.⁶

He added that chest CT was another tool, which could be used more effectively upstream to advance the study of early COPD.

As well as helping with phenotyping COPD, it could also detect other abnormalities including comorbidities of the heart.

Professor Celli decried the lack of clinical trials done worldwide in people whose COPD was not related to smoking but due to indoor and outdoor air pollution or occupational exposures.

Many of these people would be in the group of people with undiagnosed and early COPD, he said.

References

1. Agusti A & Hogg J. Update on the Pathogenesis of Chronic Obstructive Pulmonary Disease. NEJM. 2019; 381:1248-56.
2. Agusti A et al. Lung function in early adulthood and health in later life: a transgenerational cohort analysis. Lancet Respir Med. 2017; 5(12):935-45.
3. August A and Faner R. Lung function trajectories in health and disease.  Lancet Respiratory Medicine. 2019; 7(4):358-64.
4. Agusti A et al. Chronic Airway Diseases Early Stratification (CADSET): a new ERS Clinical Research Collaboration. Eur Respir J. 2019; 53(3): pii: 1900217.
5. Petersen H et al. The Course of Lung Function in Middle Aged Heavy Smokers: Incidence and Time to Early Onset of COPD. AJRCCM. 2018; 198 (11):1449-51.
6. Celli B & Wedzicha J. Update on Clinical Aspects of Chronic Obstructive Pulmonary Disease. NEJM. 2019: 381:1257-66.