Why we should never ignore an "isolated" low lung diffusing capacity.

BACKGROUND

Different diseases causing “opposite” consequences on lung function tests (obstruction vs. restriction) frequently coexist, thereby modifying the pattern that is typical of each disorder. Untangling the underlying physiological disturbances is invariably useful to the pulmonologist.

OVERVIEW

A 72-year-old smoker (80 pack-years) was referred to advanced functional assessment due to “out-of-proportion” dyspnea relative to a normal spirometry performed by her family physician. Our spirometry results were also unremarkable; moreover, lung volumes were within normal limits with a trend to restriction. Of note, these results contrasted with severely reduced DLCO and carbon monoxide transfer coefficient [KCO = DLCO/alveolar volume (VA); Figure 1A]. She terminated an incremental exercise test at only 20 W due to severe dyspnea. Despite moderate hypoxemia and hypocapnia, neither hyperinflation nor critical inspiratory constraints were observed. The dead space (VD)/tidal volume (VT) ratio was markedly increased at rest (0.60) and during exercise (0.50) in association with severe ventilatory inefficiency (VE/VCO2 nadir = 62). HRCT scanning uncovered combined pulmonary fibrosis and emphysema (CPFE; Figure 1B).

Figure 1

Pulmonary function test results (in A) and high-resolution CT scans of the chest (in B) in a 72-year-old female with “out-of-proportion” dyspnea. Pred: predicted value; Pred LL: lower limit of predicted value; pred UL: upper limit of predicted value; IC: inspiratory capacity; FRCpl: functional residual capacity by plethysmography; ERV: expiratory reserve volume; RV: residual volume; and VA: alveolar volume.

Why were spirometry and body plethysmography insensitive to the profound structural abnormalities of the patient? It is apparent that the lung parenchyma with no emphysema was heavily infiltrated by fibrosis (Figure 1B). Thus, opposite mechanical abnormalities canceled out each other, the net result being “normal” flows and volumes. The restrictive abnormalities seem to be physiologically more relevant than the enlarged airspaces-despite the CT scans suggesting otherwise. Notably, low DLCO exposed the ominous effect of both diseases on gas exchange.

Exercise VE was excessive for metabolic demand because a large fraction of the breath was “wasted” in the VD, and the patient hyperventilated (low PaCO2). These phenomena might be inter-related: an enlarged VD/VT ratio is expected to increase overall (i.e. whole-lung) ventilation; thus, hyperventilation of areas with still preserved ventilation-perfusion would lead to hypocapnia-particularly in the presence of hypoxemia and other sources of increasing chemosensitivity. Of note, VA was close to TLC (VA/TLC > 0.80), indicating that the tracing gas used in the single-breath DLCO measurement did gain access to most of the enlarged airspaces seen in Figure 1B. In other words, they were still ventilated but likely not perfused, an important source of “wasted” VE. Owing to preserved inspiratory capacity, VT and VE increased markedly. In contrast, patients with such severe emphysema-but no pulmonary fibrosis-are usually hyperinflated, mechanically constrained, and hypercapnic. Thus, CPFE, paradoxically, gave her a ventilatory mechanical advantage as she could breathe from a “safe” distance from her TLC. Unfortunately, her heightened drive fueled by “wasted” VE and the vigorous efforts to keep PaCO2 at a low value provoked severe breathlessness.

CLINICAL MESSAGE

Preserved spirometric parameters and lung volumes in symptomatic patients with an interstitial or obstructive lung disease should raise the suspicion of coexistent disorders. An out-of-proportion decrease in DLCO is frequently valuable to expose the severity of functional impairment and track the progression of the underlying diseases.