The role of the pulmonary function laboratory to assist in disease management: interstitial lung disease

BACKGROUND

Interstitial lung disease (ILD) encompasses a large and heterogeneous group of diffuse parenchymal disorders which are typically associated with low lung compliance and impaired gas exchange. A comprehensive evaluation of pulmonary function (spirometry, “static” lung volumes, DLco, oxygenation) is recommended in the initial assessment and follow-up in all patients with suspected or confirmed ILD.¹

OVERVIEW

A 78-year-old never smoking woman reported a 12-year history of dry cough which had been unsuccessfully treated as secondary to gastroesophageal reflux disease. She also complained of progressive dyspnea (mMRC = 2) over the past few months. Physical examination revealed fine, Velcro-like crackles over the lower lung fields. Spirometry showed normal FEV₁ and FVC with an FEV₁/FVC ratio above normal (113% of the predicted value); conversely, TLC, RV, and DLco were all reduced (67%, 57%, and 43% predicted, respectively). Chest HRCT indicated “probable” usual interstitial pneumonia. In this context, idiopathic pulmonary fibrosis was diagnosed after careful exclusion of other conditions associated with usual interstitial pneumonia.

Pulmonary function tests (PFTs) might provide ancillary information for ILD diagnosis, being instrumental to grade severity, gauge progression, and help in treatment choices (Figure 1). The typical spirometric findings of reduced FVC with a normal or increased FEV₁/FVC ratio might not be present in the initial stages of the disease. As this pattern is not always related to restriction, confirmation with measurements of lung volumes is usually required (i.e., TLC < lower limit of normal).² A common mistake is the assumption that a preserved FVC rules out restriction: a sizeable fraction of patients with early/mild ILD-as in the present case-shows low TLC but preserved (F)VC, provided RV decreases in tandem with TLC.³ Not infrequently in mild disease, FVC is still preserved, but the mid-expiratory flows are supranormal, indicating increased lung elastic recoil. Despite spirometric values within normal range and normal-to-mildly reduced TLC, patients with mild fibrosis usually present with impaired gas transfer at rest (low DLco), leading to an excessive ventilation to the metabolic demand during cardiopulmonary exercise testing.⁴ Lower baseline FVC and DLco, and oxygen desaturation during the six-minute walk test are known predictors of poor survival.¹ Recent data indicate that a severely reduced DLco (< 40% predicted) signals multiple interconnected mechanisms (hypoxemia, low O₂ delivery, hemodynamic abnormalities, greater mechanical constraints) that jointly conspire to decrease exercise tolerance in these patients.⁵ Repeated measurements of FVC and DLco should be used in conjunction with the burden of respiratory symptoms and chest imaging to establish whether there is, or not, disease progression (Figure 1).

Figure 1
Key physiological abnormalities in patients with interstitial lung diseases (ILDs) that underpin clinical complaints and represent risk factors for poor clinical outcomes. Some caveats and limitations of pulmonary function tests (PFTs) in this context are described in the bottom. FRC: functional residual capacity; IC: inspiratory capacity; 6MWT: six-minute walk test; CPET: cardiopulmonary exercise testing; pred: predicted; yr: year; Hb: hemoglobin; V̇O₂: oxygen consumption; V̇E: ventilation; and V̇co₂: carbon dioxide production.

CLINICAL MESSAGE

“Full” PFTs (i.e., not only spirometry) associated with the six-minute walk test and, in selected cases, cardiopulmonary exercise testing, are important to ILD management across the spectrum of disease severity. Longitudinal assessment with the patient serving as the control of him/herself is paramount, paying particular attention to (F)VC in association with DLco and exertional hypoxemia.

REFERENCES

• ¹
  Rajan SK, Cottin V, Dhar R, Danoff S, Flaherty KR, Brown KK, et al. Progressive pulmonary fibrosis: an expert group consensus statement. Eur Respir J. 2023;61(3):2103187. https://doi.org/10.1183/13993003.03187-2021
  » https://doi.org/10.1183/13993003.03187-2021
• ²
  Neder JA, O'Donnell DE, Berton DC. Practical challenges of diagnosing obstruction in the presence of restriction. J Bras Pneumol. 2019;45(5): e20190318. https://doi.org/10.1590/1806-3713/e20190318
  » https://doi.org/10.1590/1806-3713/e20190318
• ³
  Neder JA. Functional respiratory assessment: some key misconceptions and their clinical implications. Thorax. 2021;76(7):644-646. https://doi.org/10.1136/thoraxjnl-2020-215287
  » https://doi.org/10.1136/thoraxjnl-2020-215287
• ⁴
  Smyth RM, Neder JA, James MD, Vincent SG, Milne KM, Marillier M, et al. Physiological underpinnings of exertional dyspnoea in mild fibrosing interstitial lung disease. Respir Physiol Neurobiol. 2023;312:104041. https://doi.org/10.1016/j.resp.2023.104041
  » https://doi.org/10.1016/j.resp.2023.104041
• ⁵
  Smyth RM, James MD, Vincent SG, Milne KM, Marillier M, Domnik NJ, et al. Systemic Determinants of Exercise Intolerance in Patients With Fibrotic Interstitial Lung Disease and Severely Impaired DLCO. [published online ahead of print, 2023 Aug 29]. Respir Care. 2023;respcare.11147. https://doi.org/10.4187/respcare.11147
  » https://doi.org/10.4187/respcare.11147

Publication Dates

• Publication in this collection
  17 Nov 2023
• Date of issue
  2023