Impaired lung diffusing capacity for nitric oxide and alveolar-capillary membrane conductance results in oxygen desaturation during exercise in patients with cystic fibrosis

Wheatley, Courtney M.; Foxx-Lupo, William T.; Cassuto, Nicholas A.; Wong, Eric C.; Daines, Cori; Morgan, Wayne J.; Snyder, Eric M.

doi:10.1016/j.jcf.2010.09.006

Cited by 28 publications

(49 citation statements)

References 53 publications

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“…While DL CO can be influenced by both D M and V C , DL NO is thought to be a surrogate of DM, given the affinity of hemoglobin for NO. Similar to previous studies, we have demonstrated an increase in both DL CO and DL NO with exercise in both groups (Hsia, 2002; Tamhane et al, 2001; Wheatley et al, 2011a; Wheatley et al, 2011b). We found that the AA group (which has previously been shown to have reduced ENaC activity) had a greater percent increase in DL CO , DL NO , and DL CO /VA with exercise (endogenous β 2 -adrenergic stimulation) as compared to the AT/TT group.…”

Section: Discussionsupporting

confidence: 91%

“…DL CO , DL NO , and Q̇ were measured in an upright and seated position using the rebreathe technique, with gases sampled by a mass spectrometer (Perkin Elmer MGA-1100, Wesley, MA) and NO analyzer (Seivers Instruments, Boulder, CO) integrated with custom analysis software, as described previously(Snyder et al, 2006b; Snyder et al, 2005; Wheatley et al, 2011a; Wheatley et al, 2011b). Subjects breathed into a five-liter rebreathe bag containing 0.7% acetylene, 9% helium, 0.3% carbon monoxide (C 18 O), 40 PPM NO, and 35% O 2 with a respiratory rate controlled at 32 breaths per minute via metronome.…”

Section: Methodsmentioning

confidence: 99%

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Genetic variation of αENaC influences lung diffusion during exercise in humans

Baker

Wheatley

Cassuto

et al. 2011

Respiratory Physiology & Neurobiology

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Exercise, decompensated heart failure, and exposure to high altitude have been shown to cause symptoms of pulmonary edema in some, but not all, subjects, suggesting a genetic component to this response. Epithelial Na+ Channels (ENaC) regulate Na+ and fluid reabsorption in the alveolar airspace in the lung. An increase in number and/or activity of ENaC has been shown to increase lung fluid clearance. Previous work has demonstrated common functional genetic variants of the α-subunit of ENaC, including an A→T substitution at amino acid 663 (αA663T). We sought to determine the influence of the T663 variant of αENaC on lung diffusion at rest and at peak exercise in healthy humans. Thirty healthy subjects were recruited for study and grouped according to their SCNN1A genotype [n= 17vs.13, age=25±7vs.30±10yrs., BMI= 23±4vs.25±4kg/m2, V̇O2peak= 95±30vs.100±31%pred., mean±SD, for AA (homozygous for αA663) vs. AT/TT groups (at least one αT663), respectively]. Measures of the diffusing capacity of the lungs for carbon monoxide (DLCO), the diffusing capacity of the lungs for nitric oxide (DLNO), alveolar volume (VA), and alveolar-capillary membrane conductance (DM) were taken at rest and at peak exercise. Subjects expressing the AA polymorphism of ENaC showed a significantly greater percent increase in DLCO and DLNO, and a significantly greater decrease in systemic vascular resistance from rest to peak exercise than those with the AT/TT variant (DLCO=51±12vs.36±17%, DLNO=51±24vs.32±25%, SVR=−67±3vs.−50±8%, p<0.05). The AA ENaC group also tended to have a greater percent increase in DLCO/VA from rest to peak exercise, although this did not reach statistical significance (49±26vs.33±26%, p=0.08). These results demonstrate that genetic variation of the α-subunit of ENaC at amino acid 663 influences lung diffusion at peak exercise in healthy humans, suggesting differences in alveolar Na+ and, therefore, fluid handling. These findings could be important in determining who may be susceptible to pulmonary edema in response to various clinical or environmental conditions.

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Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Genetic variation of αENaC influences lung diffusion during exercise in humans

Baker

Wheatley

Cassuto

et al. 2011

Respiratory Physiology & Neurobiology

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“…The first visit was a screening visit where baseline spirometry and a maximal exercise test were performed. The findings regarding the CF patients’ responses to exercise in comparison to healthy subjects has been described previously 25. On the second visit, subjects completed baseline measurements of pulmonary function, diffusion of the lungs for carbon monoxide and nitric oxide (DLCO/DLNO), and a 25-minute EBC collection.…”

Section: Methodsmentioning

confidence: 99%

“…We followed the baseline and 30-, 60-, 90-minutes post-nebulization EBC collections with measures of the diffusion capacity of the lungs for carbon monoxide and nitric oxide (DLCO/DLNO) using a rebreathing technique described previously 29–32. Briefly, a 5-liter anesthesia bag was filled with 1575 mL of gas containing 0.7% acetylene, 9% helium 9% He, 0.3% carbon monoxide (C 18 O), 35% O 2 and 40 PPM NO (diluted immediately before the test in the bag from an 800 PPM gas mixture).…”

Section: Methodsmentioning

confidence: 99%

Exhaled Breath Condensate Detects Baseline Reductions in Chloride and Increases in Response to Albuterol in Cystic Fibrosis Patients

Wheatley

Morgan

Cassuto

et al. 2013

Clin Med Insights Circ Respir Pulm Med

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Impaired ion regulation and dehydration is the primary pathophysiology in cystic fibrosis (CF) lung disease. A potential application of exhaled breath condensate (EBC) collection is to assess airway surface liquid ionic composition at baseline and in response to pharmacological therapy in CF. Our aims were to determine if EBC could detect differences in ion regulation between CF and healthy and measure the effect of the albuterol on EBC ions in these populations. Baseline EBC Cl−, DLCO and SpO2 were lower in CF (n = 16) compared to healthy participants (n = 16). EBC Cl− increased in CF subjects, while there was no change in DLCO or membrane conductance, but a decrease in pulmonary-capillary blood volume in both groups following albuterol. This resulted in an improvement in diffusion at the alveolar-capillary unit, and removal of the baseline difference in SpO2 by 90-minutes in CF subjects. These results demonstrate that EBC detects differences in ion regulation between healthy and CF individuals, and that albuterol mediates increases in Cl− in CF, suggesting that the benefits of albuterol extend beyond simple bronchodilation.

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“…This difference is increased during exercise. Peak SaO 2 , during exercise, is related to D L NO [ 20 ]. • Fontan patients ( n = 87) and healthy controls ( n = 9).…”

Section: Selected Findingsmentioning

confidence: 99%

Lung Function Testing, Spirometry, Diffusion Capacity and Interpretation

Madsen

Mortensen

Hanel

et al. 2014

Mechanics of Breathing

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Lung function covers several physiological measures of respiratory function and structure. Ventilation, distribution of ventilation, gas diffusion, and lung perfusion are the most common terms.Measurement of lung function is used for diagnostics, monitoring, and research, but irrespective of the purpose, the methods, i.e., equipment and measurement technique, must be standardized [ 1 ] and must be subjected to continuous quality control. SpirometryFEV 1, FVC, FEV 6 , VC, and PEF

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Impaired lung diffusing capacity for nitric oxide and alveolar-capillary membrane conductance results in oxygen desaturation during exercise in patients with cystic fibrosis

Abstract: These results suggest a limitation in exercise-mediated increases in membrane conductance in CF which may contribute to a drop in SaO(2) and that resting DLNO can account for a large portion of the variability in SaO(2).

Cited by 28 publications

References 53 publications

Genetic variation of αENaC influences lung diffusion during exercise in humans

Genetic variation of αENaC influences lung diffusion during exercise in humans

Exhaled Breath Condensate Detects Baseline Reductions in Chloride and Increases in Response to Albuterol in Cystic Fibrosis Patients

Lung Function Testing, Spirometry, Diffusion Capacity and Interpretation

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