Hanna Sjöberg Ovenholm – Institutionen för kliniska vetenskaper Malmö

Title: Small airways dysfunction with special emphasis on the distribution of ventilation

Main supervisor: Viktor Hamrefors

Reviewers: Henrik Engblom, David Aronsson

Abstract

Background and aim

The small airways are often affected early in development of both asthma and COPD. However, dynamic spirometry reflects pathological changes in the small airways poorly. 

The purpose of this project is to increase knowledge about methods reflecting the small airways, and the significance of those potential changes.

Research questions 

The project covers four specific questions assessed in three study populations.

1.In the first study, we studied how the ventilation distribution (evaluated through the ratio alveolar volume (V_A) / total lung capacity (TLC)) related to airway symptoms and other lung function variables in ever smokers and individuals with mild COPD.

The material used was Role Of Low Lung function Study (ROLLS), consisting 450 individuals examined 2004-2007. 

2. In the second study, we study how the ventilation distribution and degree of emphysema in relation to impulse oscillometry parameters differ between individuals with smoking-induced COPD and individuals with alpha-1-antitrypsin deficiency.

The study cohort consists of 48 individuals with either smoking induced COPD or alpha-1-antitrypsin deficiency, examined 2015-2017.

3. In the third study we aim to evaluate if individuals with decreased V_A/TLC and moderate- severe COPD have more symptoms than those with normal V_A/TLC and equal airflow obstruction. 

The study material is collected in Uppsala 2014-2016 in the Tool Identifying Exacerbations in COPD (TIE) study, consisting approximately 150 individuals with COPD. 

4. For the fourth study we aim to re-examine the subjects in ROLLS to evaluate if decreased ratio V_A/TLC, impulse oscillometry and various lungfunction parameters are predictive for future morbidity and mortality.

Results

1. Within the group of individuals with a normal ratio FEV₁/VC, those with a low ratio V_A/TLC have a higher prevalence of respiratory symptoms compared to those with a normal V_A/TLC ratio.
    
2. Preliminary: Individuals with alpha-1-antitrypsin deficiency and individuals with smoking induced COPD have a discrepancy in oscillometry values (reactance) at the same level of emphysema.

Significance

1. These findings indicates that a low ratio V_A/TLC might reveal early airway disease in subjects without spirometric evidence of airflow obstruction.
2. Preliminary: These findings indicate that impulse oscillometry might be used for better phenotyping of emphysema. 

Published studies

Hanna Ovenholm, Suneela Zaigham, Sophia Frantz, Ulf Nihlén, Per Wollmer, Viktor Hamrefors, Inhomogeneity of ventilation in smokers and mild COPD assessed by the ratio of alveolar volume to total lung capacity, Respiratory Medicine, Volume 222, 2024, 107524, ISSN 0954-6111,

https://doi.org/10.1016/j.rmed.2023.107524.