Global Respiratory Health

Tiny Airways, Big Impact

The damage of the small airways of the lungs can result in inflammation, structural changes, and increased airway resistance. This is a common characteristic of chronic respiratory diseases such as asthma or chronic obstructive pulmonary disease (COPD). While the small airways of the lungs may not be the star of the show, they are a crucial part of the lung health story.

Spirometry: The Lung Detective

Small airways obstruction (SAO) can be detected using spirometry. Traditionally, the mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FEF_25-75) is the preferred parameter. However, novel parameters such as the forced expiratory volume in 3 seconds as a ratio of the forced expiratory volume in 6 seconds (FEV₃/FEV₆), have proven effective at detecting SAO.

We know that chronic respiratory diseases are leading causes of mortality around the world. Can SAO, even without ticking all the boxes for a doctor diagnosis of respiratory disease, predict death?

The big UK Biobank Study: What did we find?

We analysed the data of over 250,000 participants from the UK, who had high quality spirometry, and found some novel results:

• About 24% of participants had SAO. Among these, about 10% had isolated SAO, meaning their small airways were obstructed, but their larger airways were not.
• People with SAO had increased risk of death from all causes, including respiratory diseases, cardiovascular diseases, and cancers. The risk was especially high for respiratory diseases, with more than double compared to those without SAO.
• Even without respiratory disease (isolated SAO), the mortality risk was increased for cardiovascular diseases and cancers. Importantly, these findings were also true among people who have never smoked, indicating that SAO itself, regardless of smoking, is a critical factor.

  

Why should we care?

1. Early Detection: Catching SAO early could be crucial in preventing more severe lung diseases later in life.
2. Lifestyle Factors: Smoking is a big no-no for lung health, but even people who have never smoked can have SAO. This is likely to be caused by other factors.

While the UK Biobank cohort’s lack of representativeness and the relatively short follow-up period pose limitations, the study’s large sample size adds significant weight to the findings. Future research should aim to replicate these results in more diverse populations and explore the underlying mechanisms linking SAO to increased mortality.

Take home message.

Understanding and detecting SAO can give us a head start in managing chronic respiratory diseases such as COPD and asthma. Ultimately, this can aid to reduce respiratory morbidity worldwide. The findings of this study were published in the peer-reviewed journal CHEST. The article can be freely accessed and read here: https://doi.org/10.1016/j.chest.2024.04.016

Read Unmasking the threat of small airways obstruction in full

Chronic obstructive pulmonary disease (COPD) is a common illness of the lungs, and one of the leading causes of death globally, particularly in the poorest countries in the world. Chronic airflow obstruction (CAO) is a key characteristic of a COPD diagnosis. It is identified using a lung function test called spirometry and reflects a reduction in the flow of air through the airways, which is present even after taking inhaled medication.

In early COPD, inflammatory changes occur in the small airways. These are airways less than 2mm in diameter. Their small size makes it easier for noxious particles and gases, such as tobacco smoke, to collide with their walls, meaning they are particularly susceptible to damage. This presents an opportunity for the early detection and treatment of COPD if lung function tests can be used to identify changes in the small airways before they progress to more severe disease.

Isolated small airways obstruction (SAO) reflects a reduction in the flow of air through the small airways, measured using spirometry. We have previously shown that isolated SAO is common globally, and what’s more, individuals with isolated SAO are more likely to have respiratory symptoms than those with otherwise normal lung function. We have now conducted a further study to investigate whether individuals with isolated SAO are more likely to progress to CAO over time and have a greater decline in lung function than the rest of the population. We used data from 3957 participants of the multinational Burden of Obstructive Lung Disease (BOLD) study. Participants were from 18 sites across the world.  At their baseline visit, participants performed spirometry before and after inhalation of a bronchodilator, which is a medication designed to open the airways, and completed a health questionnaire. They repeated the same measurements at a follow-up visit.

After an average of 8 years of follow-up, we found that individuals with isolated SAO were 2 to 3 times more likely to progress to CAO and had lower lung function at follow-up compared to those with normal lung function. This was true in both males and females, even in those who had never smoked. We also found that isolated SAO is better than basic information such as smoking history, age, sex, and body mass index (BMI) to predict future CAO. To confirm these findings, we replicated our research using data from the UK Biobank study and found similar results.

We have shown that using spirometry to assess small airways function can identify those who are at risk of developing COPD, who would be classed as having normal lung function using current criteria. This has implications for the early intervention and prevention of a disease that is associated with significant morbidity and mortality globally.

The manuscript published in BMJ Open Respiratory research is available here: http://dx.doi.org/10.1136/bmjresp-2023-002056

Read Spirometric assessment of the small airways, clinically useful after all? in full

People with obstructive lung diseases, such as asthma and COPD, commonly report respiratory symptoms, including shortness of breath, chronic cough, chronic phlegm, and wheezing.  Small airways disease is an important feature of both conditions, where the airways of the lungs that are less than 2mm in diameter become narrowed due to inflammation. Damage to the small airways is thought to precede the development of more severe lung disease. Therefore, the measurement of small airways function has implications for early detection and prevention of disease. Spirometric small airways obstruction (SAO) is a term used to describe obstruction of the small airways detected using a lung function test called spirometry. We conducted a study to investigate whether people with SAO are more likely to report respiratory symptoms, have a history of cardiometabolic disease, and a lower quality of life, even in the absence of established lung disease. We used data from 21,934 participants of the multinational Burden of Obstructive Lung Disease (BOLD) study. All participants performed spirometry before and after inhalation of salbutamol, which is a medication designed to open the airways. Participants completed a questionnaire which enabled us to collect information on their history of shortness of breath, chronic cough, chronic phlegm, and wheezing, as well as cardiovascular disease, hypertension, and diabetes. They also provided us information about their physical and mental quality of life.

We found that approximately 1 in 5 participants had SAO. Participants with SAO were 2-3 times more likely to report shortness of breath, chronic cough, chronic phlegm, and wheezing compared to those without SAO. In addition, we found that participants with SAO were approximately 30% more likely to have a history of cardiovascular disease but not diabetes or hypertension. We also found that physical and mental quality of life were lower in individuals with SAO. These results were also true in people who had never smoked.

We also investigated whether these findings were true among study participants with SAO but with ‘normal’ lung function and, in general, they were. The main difference was that these participants’ quality of life was unaffected

Although the spirometry parameters used to define SAO have long been considered of little use clinically, we have shown that spirometric SAO is not only common in general populations but is associated with outcomes of clinical interest. Further studies are needed to replicate our findings, as well as to investigate whether those with SAO are more likely to develop more serious lung disease in later life.

The manuscript published in Respiratory Research is available here: https://doi.org/10.1186/s12931-023-02450-1

Read Spirometric small airways obstruction (SAO) is associated with clinically important outcomes in full

The small airways of our lungs are less than 2mm in diameter. Since the 1960s, these airways have been considered are a “quiet zone” where diseases progress unnoticed. That is until they cause symptoms and can be detected using specialist diagnostic equipment. Dysfunction or more appropriately obstruction of the small airways is a key feature of lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). A lung function test called spirometry is the most widely used method of assessing the small airways. However, it is largely unknown how common small airways obstruction is in the general population and what its likely determinants are.

We conducted a study to estimate the prevalence and associated risk factors for small airways obstruction across several world regions. We used data from the multinational Burden of Obstructive Lung Disease (BOLD) study, which included 26,500 participants from 41 study sites, across 34 countries. All participants performed spirometry before and after inhalation of salbutamol, which is a medication designed to open the airways. Participants also had their height and weight taken and completed a questionnaire which enabled us to collect information on exposures such as tobacco smoking. Due to the lack of agreement as to which spirometry parameter is best for assessing small airways obstruction, we compared results for two different parameters, the mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FEF_25-75) and the forced expiratory volume in 3 seconds as a ratio of the forced vital capacity (FEV₃/FVC).

We found that approximately one in five study participants have small airways obstruction. Prevalence estimates for individual sites varied from 5% to 33%. We identified several preventable risk factors for small airways obstruction including tobacco smoking, including passive smoking, low education level, low body mass index, working a dusty job for over ten years, family history of COPD and past tuberculosis infection. Results were similar for both FEF_25-75 and FEV₃/FVC parameters.

Small airways obstruction is relatively common in general populations around the world, with prevalence estimates greater than those of both asthma and COPD. Risk factors for small airways obstruction are like those of COPD, however, further studies are needed to corroborate our findings. It is especially important for future research to investigate whether those with SAO are more likely to develop established lung disease in later life, which could have significant implications for public health policy making.

The findings of this study were published in the open access, peer-reviewed journal The Lancet Global Health. The article can be read here: https://doi.org/10.1016/S2214-109X(22)00456-9

Read The small airways, quiet no more in full

The airways in our lungs are like the branches of a tree. At their widest they resemble the sturdy tree trunk and at their most narrow, the fragile twigs. Due to their size, these twig-like structures are called the small airways and they are easily damaged by noxious particles or gases we inhale, for example cigarette smoke. When they are damaged, our small airways become inflamed, which stops air moving freely and leads to something called small airways obstruction. In conditions like asthma and chronic obstructive pulmonary disease (COPD), small airways obstruction is common. However, evidence also suggests that this condition can occur on its own and may be a sign of future and more serious lung disease. A test called spirometry is often used to investigate whether the small airways are obstructed or not, however, there is no agreement on how best to do this.

We conducted a systematic review of the scientific literature to identify and summarise studies that measured small airways obstruction in the general population using spirometry. We extracted information from suitable studies on the choice of spirometry parameter used to measure small airways obstruction, criteria used to diagnose this condition, the proportion of people affected by it, and any factors that could be increase the odds of having this type of obstruction.

We found that only 25 studies have measured small airways obstruction in general populations around the world. Across these studies, 16 different spirometry parameters were used to measure it, along with 8 different diagnostic criteria. The proportion of people with small airways obstruction ranged from 7.5% to 45.9% and varied depending on the choice of spirometry parameter and world region. Just two studies identified potential risk factors for this type of obstruction, with cigarette smoking, passive smoking, increasing age, being women, low education level, and exposure to high levels of air pollution being the most promising.

Small airways obstruction is a common but understudied condition in general populations around the world. Risk factors for this condition appear to be similar to more established lung diseases, such as COPD. However, there is no consensus on the best spirometry parameter or diagnostic criteria to use when measuring this type of obstruction. For this reason, more research is required to identify the best measure of small airways obstruction and to assess whether having it increases the risk of future lung disease.

The findings of this study were published in the peer-reviewed journal Respiratory Research. The article can be read here: https://doi.org/10.1186/s12931-022-01990-2

Read Using spirometry to measure small airways obstruction, time for a rethink? in full