Background. Vest chest physiotherapy (VCPT) enhances airway clearance in cystic fibrosis (CF) by an unknown mechanism. Because cilia are sensitive to nitric oxide (NO), we hypothesized that VCPT enhances clearance by changing NO metabolism. Methods. Both normal subjects and stable CF subjects had pre- and post-VCPT airway clearance assessed using nasal saccharin transit time (NSTT) followed by a collection of exhaled breath condensate (EBC) analyzed for NO metabolites ( ). Results. VCPT shorted NSTT by 35% in normal and stable CF subjects with no difference observed between the groups. EBC concentrations decreased 68% in control subjects after VCPT (before = 115 ± 32?μM versus after = 37 ± 17?μM; ). CF subjects had a trend toward lower EBC . Conclusion. We found an association between VCPT-stimulated clearance and exhaled levels in human subjects. We speculate that VCPT stimulates clearance via increased NO metabolism. 1. Introduction Percussive chest physiotherapy (CPT) is the principal treatment that patients use to facilitate clearance of airway secretions with cystic fibrosis (CF) or other causes of bronchiectasis. Patients have historically used various forms of clapping or mechanical percussion to accomplish this. A number of devices, collectively referred to as vest chest physiotherapy (VCPT), are now available that allow patients to perform airway clearance without the aid of a second person to apply the therapy [1]. Several studies demonstrate the superiority of chest physiotherapy over no chest physiotherapy with regard to clinical outcomes [2]. Chest physiotherapy increases mucus clearance as assessed by mucus volume measurements [3]. The mechanism by which percussive chest physiotherapy modalities enhance airway clearance is not known. Clinicians hypothesize that percussion and shaking loosen adherent mucus and biofilms from the airway surface, making it easier for cough clearance to remove them from the airways. Alternatively, a number of investigators have shown that mechanical stimulation of certain tissue types results in increased epithelial cell release of NO [4]. Because mechanical stimulation increases NO release and airway clearance [5], we hypothesized that VCPT alters metabolism of NO, as measured by oxides of nitrogen ( ) release from the human airway, and is associated with enhanced airway clearance. To test these hypotheses, we measured nasal saccharin transit time (NSTT) and in exhaled breath condensate (EBC) in subjects with and without CF, before and after a therapy session with the VCPT. 2. Materials and Methods This study
References
[1]
P. A. Flume, K. A. Robinson, B. P. O'Sullivan et al., “Cystic fibrosis pulmonary guidelines: airway clearance therapies,” Respiratory Care, vol. 54, no. 4, pp. 522–537, 2009.
[2]
C. van der Schans, A. Prasad, and E. Main, “Chest physiotherapy compared to no chest physiotherapy for cystic fibrosis,” Cochrane Database of Systematic Reviews, no. 2, p. CD001401, 2000.
[3]
L. G. Hansen and W. J. Warwick, “High-frequency chest compression system to aid in clearance of mucus from the lung,” Biomedical Instrumentation and Technology, vol. 24, no. 4, pp. 289–294, 1990.
[4]
W. M. Abraham, A. Ahmed, I. Serebriakov et al., “Whole-body periodic acceleration modifies experimental asthma in sheep,” American Journal of Respiratory and Critical Care Medicine, vol. 174, no. 7, pp. 743–752, 2006.
[5]
W. M. Abraham, A. Ahmed, I. Serebriakov, et al., “Periodic acceleration via nitric oxide release modifies antigen-induced airway responses in sheep,” American Journal of Respiratory and Critical Care Medicine, vol. 169, article A321, 2004.
[6]
D. Bilton, G. Canny, S. Conway et al., “Pulmonary exacerbation: towards a definition for use in clinical trials. Report from the EuroCareCF Working Group on outcome parameters in clinical trials,” Journal of Cystic Fibrosis, vol. 10, no. 2, pp. S79–S81, 2011.
[7]
J. H. Sisson, A. J. Yonkers, and R. H. Waldman, “Effects of guaifenesin on nasal mucociliary clearance and ciliary beat frequency in healthy volunteers,” Chest, vol. 107, no. 3, pp. 747–751, 1995.
[8]
F. Hoffmeyer, M. Raulf-Heimsoth, and T. Bruning, “Exhaled breath condensate and airway inflammation,” Current Opinion in Allergy and Clinical Immunology, vol. 9, no. 1, pp. 16–22, 2009.
[9]
B. Jain, I. Rubinstein, R. A. Robbins, K. L. Leise, and J. H. Sisson, “Modulation of airway epithelial cell ciliary beat frequency by nitric oxide,” Biochemical and Biophysical Research Communications, vol. 191, no. 1, pp. 83–88, 1993.
[10]
X. Zhan, D. Li, and R. A. Johns, “Immunohistochemical evidence for the NO cGMP signaling pathway in respiratory ciliated epithelia of rat,” Journal of Histochemistry and Cytochemistry, vol. 47, no. 11, pp. 1369–1374, 1999.
[11]
C. Xue, S. J. Botkin, and R. A. Johns, “Localization of endothelial NOS at the basal microtubule membrane in ciliated epithelium of rat lung,” Journal of Histochemistry and Cytochemistry, vol. 44, no. 5, pp. 463–471, 1996.
[12]
J. Tamaoki, A. Chiyotani, M. Kondo, and K. Konno, “Role of NO generation in β-adrenoceptor-mediated stimulation of rabbit airway ciliary motility,” American Journal of Physiology: Cell Physiology, vol. 268, no. 6, pp. C1342–C1347, 1995.
[13]
V. Suresh, J. D. Mih, and S. C. George, “Measurement of IL-13-induced iNOS-derived gas phase nitric oxide in human bronchial epithelial cells,” American Journal of Respiratory Cell and Molecular Biology, vol. 37, no. 1, pp. 97–104, 2007.
[14]
M. J. Sanderson and E. R. Dirksen, “Mechanosensitivity of cultured ciliated cells from the mammalian respiratory tract: implications for the regulation of mucociliary transport,” Proceedings of the National Academy of Sciences of the United States of America, vol. 83, no. 19, pp. 7302–7306, 1986.
[15]
G. S. Barr and A. K. Tewary, “Alteration of airflow and mucociliary transport in normal subjects,” Journal of Laryngology and Otology, vol. 107, no. 7, pp. 603–604, 1993.
[16]
S. Boitano, E. R. Dirksen, and M. J. Sanderson, “Intercellular propagation of calcium waves mediated by inositol trisphosphate,” Science, vol. 258, no. 5080, pp. 292–295, 1992.
[17]
J. A. Felix, M. L. Woodruff, and E. R. Dirksen, “Stretch increases inositol 1,4,5-trisphosphate concentration in airway epithelial cells,” American Journal of Respiratory Cell and Molecular Biology, vol. 14, no. 3, pp. 296–301, 1996.
[18]
M. Salathe, T. Lieb, and R. J. Bookman, “Lack of nitric oxide involvement in cholinergic modulation of ovine ciliary beat frequency,” Journal of Aerosol Medicine, vol. 13, no. 3, pp. 219–229, 2000.
[19]
J. Alberty, W. Stoll, and C. Rudack, “The effect of endogenous nitric oxide on mechanical ciliostimulation of human nasal mucosa,” Clinical and Experimental Allergy, vol. 36, no. 10, pp. 1254–1259, 2006.
[20]
H. Grasemann, I. Ioannidis, R. P. Tomkiewicz, H. de Groot, B. K. Rubin, and F. Ratjen, “Nitric oxide metabolites in cystic fibrosis lung disease,” Archives of Disease in Childhood, vol. 78, no. 1, pp. 49–53, 1998.