Airway surface pH in subjects with cystic fibrosis

McShane, D.; Davies, Jane; Davies, Martin; Bush, Andrew; Geddes, Duncan M.; Alton, Eric W.F.W.

doi:10.1183/09031936.03.00027603

Cited by 115 publications

(104 citation statements)

References 33 publications

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“…7), acetate and butyrate (online supplementary figs S3 and S4) inhibited P. aeruginosa growth over ⩾6 h. In contrast, we saw that low concentrations of SCFAs resulted in enhanced bacterial growth, particularly during the mid-log phase of growth. Cystic fibrosis airway secretions have been shown to have a slightly acidic pH [23], although this observation is controversial [24]. As SCFAs have a higher proportion of protonated species in acidic conditions, their diffusion through membranes is greatly enhanced [7].…”

Section: Resultsmentioning

confidence: 99%

Short-chain fatty acids affect cystic fibrosis airway inflammation and bacterial growth

et al. 2015

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The hypoxic environment of cystic fibrosis airways allows the persistence of facultative anaerobic bacteria, which can produce short-chain fatty acids (SCFAs) through fermentation. However, the relevance of SCFAs in cystic fibrosis lung disease is unknown. We show that SCFAs are present in sputum samples from cystic fibrosis patients in millimolar concentrations (mean±SEM 1.99±0.36 mM).SCFAs positively correlated with sputum neutrophil count and higher SCFAs were predictive for impaired nitric oxide production. We studied the effects of the SCFAs acetate, propionate and butyrate on airway inflammatory responses using epithelial cell lines and primary cell cultures. SCFAs in concentrations present in cystic fibrosis airways (0.5-2.5 mM) affected the release of granulocytemacrophage colony-stimulating factor, granulocyte colony-stimulating factor and interleukin (IL)-6. SCFAs also resulted in higher IL-8 release from stimulated cystic fibrosis transmembrane conductance regulator (CFTR) F508del-mutant compared to wild-type CFTR-corrected bronchial epithelial cells. At 25 mM propionate reduced IL-8 release in control but not primary cystic fibrosis epithelial cells. Low (0.5-2.5 mM) SCFA concentrations increased, while high (25-50 mM) concentrations decreased inducible nitric oxide synthase expression. In addition, SCFAs affected the growth of Pseudomonas aeruginosa in a concentration-and pH-dependent manner.Thus, our data suggest that SCFAs contribute to cystic fibrosis-specific alterations of responses to airway infection and inflammation. @ERSpublications Short-chain fatty acids contribute to CF-specific alterations of responses to airway infection and inflammation

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Section: Resultsmentioning

confidence: 99%

Short-chain fatty acids affect cystic fibrosis airway inflammation and bacterial growth

et al. 2015

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“…The pH of the airway in health has been reported to be slightly alkaline (pH in the range of 7-8) [5][6][7][8]. In states of acute lung disease, where a knowledge of airway chemistry would be most beneficial, the invasiveness of most sampling techniques have precluded even experimental assessment of the airway environment.…”

Section: Discussionmentioning

confidence: 99%

Exhaled breath condensate pH is a robust and reproducible assay of airway acidity

et al. 2003

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Exhaled breath condensate (EBC) pH is low in several lung diseases and it normalises with therapy.The current study examined factors relevant to EBC pH monitoring. Intraday and intraweek variability were studied in 76 subjects. The pH of EBC collected orally and from isolated lower airways was compared in an additional 32 subjects. Effects of ventilatory pattern (hyperventilation/hypoventilation), airway obstruction after methacholine, temperature (-44 to z13uC) and duration of collection (2-7 min), and duration of sample storage (up to 2 yrs) were examined. All samples were collected with a disposable condensing device, and de-aerated with argon until pH measurement stabilised.Mean EBC pH (n=76 subjects, total samples=741) was 7.7¡0.49 (mean¡SD). Mean intraweek and intraday coefficients of variation were 4.5% and 3.5%. Control of EBC pH appears to be at the level of the lower airway. Temperature of collection, duration of collection and storage, acute airway obstruction, subject age, saliva pH, and profound hyperventilation and hypoventilation had no effect on EBC pH.The current authors conclude that in health, exhaled breath condensate pH is slightly alkaline, held in a narrow range, and is controlled by lower airway source fluid. Measurement of exhaled breath condensate pH is a simple, robust, reproducible and relevant marker of disease. Eur Respir J 2003; 22: 889-894.

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“…However, in older children and adults with CF, the effect of genotype in ASL pH is more variable (44,58,74). Whether inflammation, remodeling, infection, and/or age are factors that might circumvent the loss of CFTR anion channels and increase ASL pH in CF (Fig.…”

Section: Discussionmentioning

confidence: 99%

pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37

Alaiwa¹,

Reznikov²,

Gansemer³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

181

162

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The pulmonary airways are continuously exposed to bacteria. As a first line of defense against infection, the airway surface liquid (ASL) contains a complex mixture of antimicrobial factors that kill inhaled and aspirated bacteria. The composition of ASL is critical for antimicrobial effectiveness. For example, in cystic fibrosis an abnormally acidic ASL inhibits antimicrobial activity. Here, we tested the effect of pH on the activity of an ASL defensin, human β-defensin-3 (hBD-3), and the cathelicidin-related peptide, LL-37. We found that reducing pH from 8.0 to 6.8 reduced the ability of both peptides to kill Staphylococcus aureus. An acidic pH also attenuated LL-37 killing of Pseudomonas aeruginosa. In addition, we discovered synergism between hBD-3 and LL-37 in killing S. aureus. LL-37 and lysozyme were also synergistic. Importantly, an acidic pH reduced the synergistic effects of combinations of ASL antibacterials. These results indicate that an acidic pH reduces the activity of individual ASL antimicrobials, impairs synergism between them, and thus may disrupt an important airway host defense mechanism.

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Airway surface pH in subjects with cystic fibrosis

Cited by 115 publications

References 33 publications

Short-chain fatty acids affect cystic fibrosis airway inflammation and bacterial growth

Short-chain fatty acids affect cystic fibrosis airway inflammation and bacterial growth

Exhaled breath condensate pH is a robust and reproducible assay of airway acidity

pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37

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