Lung volumes in exacerbations of asthma

doi:10.1016/0002-9343(66)90021-0

The American Journal of Medicine

Volume 41, Issue 2, August 1966, Pages 259-273

https://doi.org/10.1016/0002-9343(66)90021-0 Get rights and content

Abstract

Lung volumes and forced expiratory volume in one second (FEV₁) were measured serially in thirty patients during recovery from episodes of severe asthma. Abnormalities of lung volumes were present in all patients at some stage during the course of the illness.

Vital capacity (VC) was significantly reduced in most (but not all) patients at the time of acute dyspnoea, and improved with therapy to reach normal levels in all but two patients. Functional residual capacity (FRC) was increased above normal levels in twenty-eight patients on admission to hospital, and in some the increases were of the order of 3 to 5 L. In most patients FRC decreased with treatment, but in three it remained unchanged and in seven it increased. Residual volume (RV) showed changes similar in direction and magnitude to those of FRC. Total lung capacity (TLC) was increased by amounts up to several liters in about half the patients initially and in all of these it decreased with treatment; in the other patients it was normal on admission and either increased or remained unchanged during recovery. Gross changes in lung volumes were demonstrated in an acute episode of asthma with recovery in less than an hour.

Analysis of relative changes in TLC, FRC and inspiratory capacity (IC) during recovery from episodes of asthma, combined with a consideration of changes in the chest roentgenogram, provide a unified explanation of the lung volume changes in asthma. It is suggested that all subjects react to increased expiratory airways resistance with an increase in RV, FRC and TLC, sometimes of considerable magnitude. The measured changes of lung volume in individual subjects are influenced by the development of non-ventilated regions in the lungs which do not necessarily depend on complete airways closure or atelectasis.

The considerable increases in FRC must lead to large increases in the elastic work required in inspiration during episodes of asthma, and must account for an appreciable portion of the respiratory distress. This factor probably also accounts for the complaint of inspiratory difficulty made by some patients.

In the presence of the large changes in TLC demonstrated, measurements of FEV₁ alone do not provide a reliable index of change in the degree of airways obstruction. In particular, when TLC decreases appreciably, even a constant FEV₁ indicates a considerable lessening in the degree of airways obstruction. Adequate assessment of the response of a patient to therapy requires the measurement of lung volumes as well as of FEV₁. Otherwise, objectively beneficial therapy may be withheld from patients in whom it appears to produce insignificant increases in FEV₁.

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Physiological changes also occur in the airways of individuals with asthma in response to infection. More than 5 decades ago, it was noted that significant changes in lung function occur in patients with asthma during infection, with decreases in FEV1 and forced vital capacity as well as evidence of increased air trapping.51 Animal models show that viral airway injury at an early age may induce small airway lesions that are associated with small airway physiological dysfunction, which may persist into maturity.52
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Kaminsky and Irvin5 obtained pathologic specimens in a patient with reversible restriction due to asthma and demonstrated terminal airway inflammation. In addition, increased VC without change in FEV1/VC frequently occurs in patients with asthma following bronchodilator administration (“volume responders”),47–51 supporting that reduced lung volume may be a manifestation of airway disease. The present study demonstrates that a similar physiologic pattern may be observed following WTC dust exposure.
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This is a retrospective study of 54 persistently symptomatic subjects following World Trade Center (WTC) dust exposure. Inclusion criteria were reduced vital capacity (VC), FEV₁/VC > 77%, and normal chest roentgenogram. Measurements included spirometry, plethysmography, diffusing capacity of lung for carbon monoxide (Dlco), impulse oscillometry (IOS), inspiratory/expiratory CT scan, and lung compliance (n = 16).
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This study describes a distinct physiologic phenotype of restriction due to airway dysfunction. This pattern was observed following WTC dust exposure, has been reported in other clinical settings (eg, asthma), and should be incorporated into the definition of restrictive dysfunction.
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There is further potential for disconnect with Scond when units are so poorly ventilated that they do not communicate with the mouth, which is supported by the current model. Inert gas dilution is inaccurate in predicting the lung volumes of patients with severe asthma and airway closure (Woolcock and Read, 1966); it is theoretically possible that Scond has a similar disconnect to the severity of physiological impairment if the volume of trapped gas is significant. Table 3 lists estimates of FRC from the N2 washout simulations.
Asthma is typically characterised by increased ventilation heterogeneity. This can be directly inferred from the visualisation of ventilation defects in imaging studies, or indirectly inferred from indices derived from the multiple-breath nitrogen washout (MBNW). The basis for the understanding of the MBNW indices and their implication for changes in structure and function at the largest and smallest scales in the lung has been facilitated by mathematical models for inert gas transport. A new model is presented that couples airway resistance and regional tissue compliance, for simulation of the effect of ‘patchy’ bronchoconstriction – as inferred from imaging studies – on the Scond index of ventilation heterogeneity. Patches of reduced washin gas concentration can emerge by constricting only the terminal bronchioles within localised regions, however this pattern of constriction is insufficient to affect Scond; Scond from this model is only sensitive to constriction that occurs within entire contiguous regions. Furthermore the model illustrates the possibility that the MBNW may not detect gas trapped in ventilation defects.
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Previously, we found pulmonary gas trapping to be a rapid, simple and objective measure of methacholine-induced airway obstruction in naïve mice. In this study we extended that finding by using methacholine-induced pulmonary gas trapping to differentiate airway responses of ovalbumin-sensitized, ovalbumin-exposed (Positive Control) and ovalbumin-sensitized, sodium chloride-exposed (Negative Control) mice. Additionally, pulmonary gas trapping and enhanced pause were compared following methacholine exposure in sensitized and nonsensitized mice. Finally, we examined by nose-only inhalation the ability of the glucocorticosteroid budesonide and the peroxisome proliferator-activated receptor-γ agonist ciglitazone to modify methacholine-induced airway responses in ovalbumin-sensitized mice. Positive Controls exhibited a 7.8-fold increase in sensitivity and a 2.4-fold enhancement in the maximal airway obstruction to methacholine versus Negative Controls. Following methacholine, individual Positive and Negative Control mouse enhanced pause values overlapped in 9 of 9 studies, whereas individual Positive and Negative Control mouse excised lung gas volume values overlapped in only 1 of 9 studies, and log[excised lung gas volume] correlated (P = 0.023) with in vivo log[enhanced pause] in nonsensitized mice. Finally, budesonide (100.0 or 1000.0 μg/kg) reduced methacholine-mediated airway responses and eosinophils and neutrophils, whereas ciglitazone (1000.0 μg/kg) had no effect on methacholine-induced pulmonary gas trapping, but reduced eosinophils. In conclusion, pulmonary gas trapping is a more reproducible measure of methacholine-mediated airway responses in ovalbumin-sensitized mice than enhanced pause. Also, excised lung gas volume changes can be used to monitor drug interventions like budesonide. Finally, this study highlights the importance of running a positive comparator when examining novel treatments like ciglitazone.

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^☆: This study was supported by a research fellowship and a grant in aid from the Asthma Foundation of New South Wales.

¹: From the Department of Medicine, University of Sydney, and the Thoracic Unit, Royal Prince Alfred Hospital, Sydney, Australia.

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Clinical studyLung volumes in exacerbations of asthma☆

Abstract

J. Allergy

Lancet

Am. J. Med.

Studies of total pulmonary capacity and its subdivisions. VII. Observations during the acute respiratory distress of bronchial asthma and following the administration of epinephrine

J. Clin. Invest.

Impairment of respiratory function in bronchial asthma

Clin. Sc.

Pulmonary function in children. II. Preliminary studies in chronic intractable childhood asthma

J. Allergy

Respiratory studies in children. XI. Mechanics of breathing, lung volumes and ventilatory capacity in asthmatic children from attack to symptom-free status

Acta paediat.

Respiratory Function in Disease

Clinical study
Lung volumes in exacerbations of asthma☆