Interrogating pulmonary diffusing capacity in long COVID: insights from DLCO and DLNO testing, 2025, Parks et al.

[SNT Gatchaman]

Interrogating pulmonary diffusing capacity in long COVID: insights from DLCO and DLNO testing

Spoiler: Authors

Parks, Jordan K; Johnson, Bruce D; Shea, Meredith G; Kim, Chul-Ho; Johnston, Jessica I; Carlson, Alex; Schwartz, Jesse C; Wheatley-Guy, Courtney M

INTRODUCTION
The lingering respiratory effects of COVID-19, particularly in patients with Long COVID, remain poorly understood, prompting a comprehensive evaluation of lung function in this population.

METHODS
Simultaneous measurements of diffusion capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO), chest computed tomography (CT), lung ultrasound and questionnaires were collected in 74 subjects. Participants were categorized into two groups: those that have no lingering symptoms (NS, n = 37) and those still struggling with symptoms after initial infection, the disease known as Long COVID (LC, n = 37).

RESULTS
DLCO and DLNO were significantly lower in the LC group compared to the NS group (LC vs. NS, DLCO: 25.94 ± 7.65 vs. 21.71 ± 6.35 mL/min/mmHg, p = 0.009; DLNO: 148.5 ± 35.6 vs. 126.6 ± 32.2 mL/min/mmHg, p = 0.006). Pulmonary capillary blood volume (Vc) was also significantly lower in the LC group (43.38 ± 13.87, 70.79 ± 17.77, p = 0.003; LC vs. NS, respectively). Alveolar volume (VA) is significantly lower in the LC group (LC vs. NS, 5.06 ± 1.17 vs. 5.95 ± 1.16, p = 0.004). There was no significant difference between groups for surface area of the lungs available for gas exchange by resistance to gas transfer across the alveolar-capillary membrane (DM) between groups (LC vs. NS, 208.63 ± 97.3, 223.0 ± 93.47 mL/min/mmHg, p = 0.54). These findings indicate that Vc is the driving factor of decreased DLCO. CT findings and lung ultrasound showed no differences between the two groups for lung fluid (p = 0.525; p = 0.298).

CONCLUSION
These findings suggest that a lack of volume available for perfusion could be problematic for these patients and as such requires further investigation for clinical management of these patients.

Web | DOI | PDF | Frontiers in Physiology | Open Access

 

[Eleanor]

Limitations section (line breaks added)

This study recognizes that pulmonary function values prior to infection were not available, and it is therefore uncertain if the results of the pulmonary function testing would highlight differences in susceptibility to developing LC versus a decline in values caused by acute infection that later developed into LC.

Furthermore, this study population had a very large range of LC symptom burden, spanning from mild to life debilitating and likewise a large range of treatment methods dependent on severity of acute infection, spanning from over-the-counter medications to hospitalization with mechanical ventilation. The study had very limited exclusion criteria and as such did not account for comorbidities in the subject group. When evaluating for covariates of age, sex and BMI, there was no longer a significant difference between groups.

This analysis revealed that sex was a primary driver of differences in diffusion capacity and Vc, with females with LC showing significantly lower DLNO and Vc compared to their non-LC counterparts. Where as in males, there was no difference based on disease status. Nevertheless, unadjusted analyses indicate that patients with LC tend to have lower diffusion capacity compared with controls that warrant careful consideration alongside these known confounders.

Due to influence of covariates on the findings, particularly sex, and our small sample size, there is limited statistical power and adjustments for all possible confounders were limited. Future research should address these limitations by enrolling a large sample size to allow for confirmation of our findings and evaluation of other confounders.

 

[richie]

Sorry if this question is slightly off topic. Can anyone tell me how "normal %" is arrived at in PFT's? Is it that ca 100% of the general population with say 80% expected TLCO etc are asymptomatic or is it that 80% of healthy controls are asymptomatic or is it that 80% of the pateint population with say sarcoid have no classical restrictive symptoms at 80% values? How are they deriving "normality"? Can one map over from healthies and how can it be said that those with a lung pathology have no symptoms deriving from the condition giving the 80% score - not all symptoms are classical in many conditions. Same question might be asked re. any cut off test.

 

[Utsikt]

Limitations section (line breaks added)

When evaluating for covariates of age, sex and BMI, there was no longer a significant difference between groups.

Seems like an important caveat!

 

[SNT Gatchaman]

See also Symptomatic post COVID patients have impaired alveolar capillary membrane function and high VE/VCO2 (2024)

 

[Eleanor]

Sorry if this question is slightly off topic. Can anyone tell me how "normal %" is arrived at in PFT's? Is it that ca 100% of the general population with say 80% expected TLCO etc are asymptomatic or is it that 80% of healthy controls are asymptomatic or is it that 80% of the pateint population with say sarcoid have no classical restrictive symptoms at 80% values? How are they deriving "normality"?

Sorry, this isn't a direct reply to your question but might be relevant re 'normal values'. The authors say:

Interestingly, DLCO is still considered normal in many of the LC patients in our study, with normal DLCO values being >75% of predicted (Modi and Cascella, 2020). Perhaps this is why patients with LC tend to appear normal on pulmonary function testing but still have unexplained symptoms. Although this study does not have subject data prior to COVID infections, it would be reasonable to suspect that even a low normal DLCO value could be a significant decline for some subjects leading them to feel symptomatic. This decline to low normal DLCO and DLNO data can be supported with results from the questionnaires collected.

SGRQ was given to assess pulmonary related symptoms and was shown to have a significant negative relationship with DLCO, DLNO, Vc and GxCap.

SGRQ is the St. George’s respiratory questionnaire, which evaluates 'symptoms related to pulmonary changes including dyspnea, coughing, and wheezing'.

 

[richie]

Sorry, this isn't a direct reply to your question but might be relevant re 'normal values'. The authors say:





SGRQ is the St. George’s respiratory questionnaire, which evaluates 'symptoms related to pulmonary changes including dyspnea, coughing, and wheezing'.

Yes there are a fair few sarcoid doctors who consider decline to be important in causing symptoms .