Diffusion capacity of the lungs for carbon monoxide (DLCO) testing is used to assess the transfer of gases from the alveoli into the bloodstream. Abnormal DLCO results can help diagnose, distinguish, and manage cardiopulmonary diseases such as asthma.

By Bill Pruitt, MBA, RRT, CPFT, FAARC 


Diffusion capacity of the lungs for carbon monoxide (DLCO) testing is used to assess the transfer of gases from the alveoli into the bloodstream. Abnormal DLCO results can help diagnose and/or manage cardiopulmonary diseases such as asthma.

This article will explore the use of DLCO testing in assessing lung function and lung health in asthma patients, best practices for accurate testing and interpretation, and some of the DLCO technology available.

Asthma Overview

Asthma is pulmonary disease characterized by chronic airway inflammation and usually associated with airway hyper-responsiveness (“twitchy airways”). According to the 2023 update of the Global Initiative for Asthma (GINA), asthma is defined by a history of symptoms such as wheezing, shortness of breath, feeling chest tightness, and cough, along with a limitation of expiratory airflow brought on by bronchospasm.1

Asthma symptoms and airflow limitation that are present during an asthma flare-up may resolve spontaneously or after treatment with medications. Some patients may show no signs or symptoms of asthma for weeks or months, while others with more severe asthma may have frequent symptoms—even to the point of dealing with asthma on a daily basis.1 Asthma has several recognized phenotypes including allergic asthma, non-allergic asthma, adult-onset asthma, asthma associated with persistent airflow limitation, and asthma associated with obesity.

Diagnosing Asthma

Asthma is diagnosed based on a history of symptoms (and the pattern of the symptoms) and spirometry findings that show variable (reversible) airflow obstruction. Asthma symptoms are often worse at night or early in the morning, vary in intensity and in timing, and may be linked to viral infections (ie, common cold, influenza, RSV), exercise, exposure to allergens, changes in weather, or exposure to irritants (ie, car exhaust, air pollution, smoke, strong smells).

When a history of symptoms are present, expiratory airflow response to a bronchodilator is checked using spirometry to measure pre/post Forced expiratory volume in one second (FEV1). The FEV1 is measured by coaching the patient to take in a rapid deep breath to reach total lung capacity (TLC) then forcefully blasting out. Usually, the forced expiration is continued until reaching residual volume which provides a measurement of both the FEV1 and the forced vital capacity (FVC). An increase in FEV1 by >12% and 200 mL from the baseline after administration of an inhaled bronchodilator (pre/post spirometry) is considered a positive test and shows reversibility of the airflow obstruction.1

When a patient’s initial spirometry is normal, a bronchial challenge test (BCT) is often done to check for a hyper-responsive response to the challenge. A positive BCT is another way to confirm asthma and may be performed by exercise, hyperventilation, or using inhaled agents such as methacholine, hypertonic saline, or mannitol. A positive BCT will show a drop in FEV1 from baseline as a result of the challenge.

Distinguishing Asthma from Other Diseases

Making a definitive diagnosis of asthma can be difficult since many other lung diseases share many of the same symptoms (consider emphysema as it relates to cough, shortness of breath, and wheezing). GINA 2023 states that in some 12% to 50% of patients thought to have severe asthma, the asthma diagnosis is not correct.1

Patients with long-standing asthma and chronic inflammation may have airway remodeling occur to the point that airway reversibility no longer occurs in pre/post spirometry and expiratory airflow limitation is persistent. In other patients, both asthma and COPD are present (described as asthma-COPD overlap syndrome of ACOS). These patients have many or most of the following symptoms: difficulty breathing, excess mucus (more than usual), feeling tired, frequent coughing, frequent shortness of breath, and wheezing.2

Common diseases that need to be considered when trying to diagnose asthma include: 3

  • COPD
  • Infectious diseases (bacterial, viral, or fungal)
  • Gastroesophageal reflux disease (GERD)
  • Chronic rhinosinusitis (CRS)
  • Congestive heart failure (CHF)
  • Vocal cord dysfunction & other upper airway disorders

There are many more diseases to be considered in the differential diagnosis of asthma.3 

Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)

DLCO testing provides insight into the pulmonary system’s function of transferring gases in the alveoli across the alveolar/capillary (A/C) membrane into the capillary blood and into the red blood cells (RBC). DLCO is also referred to as the transfer factor for carbon monoxide or TLCO.4

The DLCO test uses a mixture of gases containing air, carbon monoxide, and a tracer gas (ie, helium) to determine the transfer of gas from alveoli to RBC. Carbon monoxide (CO) behaves much like oxygen and is quickly picked up in the RBC by hemoglobin. The tracer gas is used in the DLCO test to measure alveolar volume.

Factors that can alter the diffusion or transfer of gases include changes in the A/C membrane, changes in hemoglobin, and capillary blood volume.4 It has been thought that thickening of the A/C membrane found in interstitial lung disease (ie, pulmonary fibrosis) and a reduction in A/C membrane surface area found in emphysema reduce the DLCO, but more recently the theory in reduction in DLCO may be driven in these diseases by a reduction in the volume of RBCs in the pulmonary capillary bed.4 According to an article on DLCO in the UpToDate website, “In general, the DLCO is used to identify the cause of dyspnea or hypoxemia, monitor disease progression in interstitial lung disease, and identify pulmonary hypertension in patients at risk, such as those with systemic sclerosis.” 4

DLCO Testing

Almost all pulmonary function testing labs use the single-breath method for performing the DLCO test. Performance of the test is fairly easy and most patients can do this test without issues. The patient is seated and wears a nose clip during the test. After a short period of resting breathing, the test begins with having the patient perform a full exhalation to reach residual volume followed by a rapid inhalation of the test gas mixture (containing 0.3% CO, 10% helium, 21% oxygen, balance nitrogen) to reach total lung capacity (TLC). There is a 10-second breath hold at TLC, then the patient exhales quickly and completely to reach residual volume. 

As the test gases are being inhaled, and during the breath hold, CO and the tracer gas diffuse through the A/C membrane and CO attaches to the hemoglobin. During the full exhalation from TLC and immediately after dead space gases are exhaled, a sample of the exhaled gases is collected and analyzed to determine the uptake of the CO and a measurement of the alveolar volume by the dilution of the tracer gas. In 2017 the European Respiratory Society and the American Thoracic Society (ERS/ATS) released updated standards for single-breath DLCO testing that provides a detailed description of the test, guidelines for calibration and cleaning, criteria for acceptability and repeatability details on quality control.5

DLCO and Asthma

In patients with asthma, DLCO is usually normal or mildly elevated in contrast to other obstructive lung diseases (ie, COPD/emphysema) which often reflect a decrease in DLCO.6 The increased DLCO in asthma is possibly due to several factors: 6

  • Perfusion in the lung apices due to increased pulmonary arterial pressure or having a more negative pleural pressure due to bronchial narrowing;
  • Hyperinflation and increased intrathoracic pressure in patients with severe asthma;
  • Increased pulmonary capillary blood volume;
  • Increased airway vascularization which increases the capillary surface area;
  • Unlike diseases such as emphysema, asthma does not damage/destroy the alveolar walls, so the functioning alveolar surface area is intact.
  • Measuring the DLCO in asthma patients is also useful in distinguishing asthma from other diseases such as emphysema and in assessing comorbid conditions such as ACOS, pulmonary hypertension, and interstitial lung disease.7 In these comorbidities the DLCO will be reduced. 

In a 2022 study published in the journal Asthma Research and Practice, researchers measured the DLCO in 122 patients who had a 30+ year history of asthma.6 The baseline characteristics and original diagnosis were established in an asthma clinic between 1974-1990, and the follow-up clinic visits from 2017-2019 provided the DLCO testing data. 103 patients were classified as having active asthma and 19 were classified as being in complete remission from asthma. No significant difference was found in the DLCO between those with active asthma compared to those in remission, but when the results were adjusted for alveolar volume (using the diffusion constant KCO derived from the ratio DLCO/alveolar volume) those with active asthma had a significant increase in DLCO. When adjusted for age and smoking history (pack-years) there was a significant increase in DLCO per year of having asthma, and when adjusted for age, smoking history, an alveolar volume there was also a significant difference in KCO per year of having asthma. The researchers reported that a longer duration of asthma being associated with an increased DLCO fits with the model of long-standing asthma resulting in airway remodeling.6

DLCO Technology

In the past, DLCO testing was done in a hospital-based pulmonary function lab, but new technology now allows measurements to be performed in the physician’s office or other locations.8 ndd Medical Technologies has two portable handheld devices that can measure DLCO (the EasyOne Pro and EasyOne Pro LAB). PulmOne USA offers a portable device (the Mini Box+) that provides DLCO plus other PFT measurements. Larger cart-based PFT machines that can perform DLCO tests are available from various companies including Vyaire with their Vyntus One Pulmonary Function System, KoKo with their PX3000 system, MGC Diagnostics with their Ultima PF pulmonary function system and Vitalograph Morgan PFT systems with their VitaloLAB system. These systems can perform a complete PFT test but the cart-based units are more expensive and more complex due to their wider scopes of testing.

Conclusion

A clear asthma diagnosis can be elusive and is often misdiagnosed unless objective testing for pulmonary function is performed. The DLCO can help rule in/out other diagnoses and, with the newer PFT systems on the market, this test can be performed in almost any setting (with the requirement that a trained operator is running the test). Patients with asthma tend to have normal or elevated DLCO results, and although pre/post spirometry is the primary test, DLCO can often bring more clarity to the situation. DLCO testing is not difficult for a patient to perform, done in a brief time frame, is noninvasive and safe, and should be considered in cases that may involve comorbid conditions or when investigating severe asthma.

RT

Bill Pruitt, MBA, RRT, CPFT, FAARC, is a writer, lecturer, and consultant. Bill has over 40 years of experience in respiratory care in a wide variety of settings and has over 20 years teaching at the University of South Alabama in Cardiorespiratory Care. Now retired from teaching, Bill continues to provide guest lectures, participates in podcasts, and writes professionally. For more info, contact [email protected].


References

  1. The Global Initiative for Asthma (GINA) 2023. https://ginasthma.org/2023-gina-main-report/#:~:text=The%202023%20update%20of%20the%20Global
  2. Asthma-COPD Overlap Syndrome (ACOS). American Lung Association. Published Sept. 2023. https://www.lung.org/lung-health-diseases/lung-disease-lookup/asthma/learn-about-asthma/types/asthma-copd-overlap-syndrome
  3. Johnson J, Abraham T, Sandhu M, Jhaveri D, Hostoffer R, Sher T. Differential diagnosis of asthma. Allergy and Asthma. 2019 Feb 23:383
  4. McCormack M. Diffusing capacity for carbon monoxide. UpToDate. Published Feb. 2024. https://www.uptodate.com/contents/diffusing-capacity-for-carbon-monoxide.
  5. Graham BL, Brusasco V, Burgos F, et al. 2017 ERS/ATS Standards for single-breath carbon monoxide uptake in the lung. Eur Respir J 2017; 49: 1600016.
  6. Schultz CU, Tupper OD, Ulrik CS. Static lung volumes and diffusion capacity in adults 30 years after being diagnosed with asthma. Asthma research and practice. 2022 Aug 4;8(1):4.
  7. Neder JA, Berton DC, Muller PT, O’Donnell DE. Incorporating lung diffusing capacity for carbon monoxide in clinical decision making in chest medicine. Clinics in Chest Medicine. 2019 Jun 1;40(2):285-305.
  8. Enright P. Office-based DLCO tests help pulmonologists to make important clinical decisions. Respiratory investigation. 2016 Sep 1;54(5):305-11.