Changes in Pulmonary Mechanics with Increasing Disease Severity in Children and Young Adults with Cystic Fibrosis

Abstract

As forced expiratory volume in 1 second (FEV(1)) is a major predictor of outcome in patients with cystic fibrosis (CF), we investigated the effect of FEV(1) on pulmonary mechanics in children and young adults with CF. We measured respiratory rate; tidal volume; minute ventilation; arterial blood gases; sniff esophageal pressure; dynamic lung compliance; total pulmonary resistance; intrinsic positive end expiratory pressure; and total, elastic, and resistive work of breathing in 32 patients (FEV(1) range: 12-49% predicted). We observed correlations between FEV(1) and Pa(O(2)) (r = 0.76, p < 0.0001) and Pa(CO(2)) (r = -0.70, p < 0.0001), FEV(1) and respiratory rate/tidal volume (r = -0.41, p = 0.02), FEV(1) and dynamic lung compliance (r = 0.64, p < 0.0001), and FEV(1) and total work of breathing (r = -0.52, p = 0.002) and elastic work of breathing (r = -0.60. p = 0.0003). No correlations were observed between FEV(1) and sniff esophageal pressure (p = 0.5), minute ventilation (p = 0.9), total pulmonary resistance (p = 0.3), intrinsic positive end expiratory pressure (p = 0.3), or resistive work of breathing (p = 0.1). As FEV(1) declines in children and young adults with CF, there is an increase in the elastic load and work of breathing, resulting in a rapid shallow breathing pattern, that is associated with further impairment of gas exchange.

Tobramycin Inhalation Powder in Cystic Fibrosis Patients: Response by Age Group

“…In addition, children demonstrate greater 'elasticity' of lung function, which declines over time. 29 As patients with CF age and the disease progresses, repeated infections and chronic P. aeruginosa infection lead to lung damage and permanent loss of lung function, which may also reduce their capacity to respond to treatment. Interestingly, in our study those with more severe disease seemed to achieve greater improvements in lung function (as measured by the change in percent-of-predicted FEV 1 from baseline) after treatment with tobramycin than those with less severe disease (see Table 2).…”

Time constant of inspiratory muscle relaxation in cystic fibrosis

“…Our study identified that FEV 1 and FVC were associated only modestly with τ in CF. The relatively modest association of τ with FEV 1 and FVC implies that high values of τ and possible respiratory failure are determined by additional factors other than spirometry. Thus, τ might be conveying information that is not readily available through other methods, and has the potential to fit an unmet clinical need in managing patients with CF.…”

“…Determinants of respiratory muscle compromise in CF have been reported in detail (1)(2)(3)9,19,20). Airway obstruction impacts on inspiratory muscle function by increasing the load against which the respiratory muscles are forced to operate (1) and hyperinflation places the respiratory muscles in mechanical disadvantage (2).…”

“…Airway obstruction impacts on inspiratory muscle function by increasing the load against which the respiratory muscles are forced to operate (1) and hyperinflation places the respiratory muscles in mechanical disadvantage (2). Moreover, malnutrition affects the diaphragmatic pressure-generating capacity (20), given that decreased somatic muscle mass indices have been consistently associated with decreased maximal respiratory pressures in CF patients (3,9).…”

In silico modeling of interstitial lung mechanics: implications for disease development and repair

“…In contrast, the fibrotic lung becomes progressively stiffer due to the deposition of collagen in the tissues [7]. This reduces lung volume and increases the work of breathing [8]. Nevertheless, the derangements in lung mechanics at the organ level accompanying emphysema [9] and fibrosis [10] are not simply determined by the amount of tissue loss or remodeling.…”