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To the Editor:To address the issues Piacentini et al1Piacentini G.L. Peroni D.G. Bodini A. Boner A.L. Exhaled nitric oxide in asthmatic children at high altitude.J Allergy Clin Immunol. 2007; 120: 1226-1227Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar have raised, we are supplying additional data regarding our trial,2Huss-Marp J. Krämer U. Eberlein B. Pfab F. Ring J. Behrendt H. et al.Reduced exhaled nitric oxide values in children with asthma after inpatient rehabilitation at high altitude.J Allergy Clin Immunol. 2007; 120: 471-472Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar which were not included in the original publication because of space limitations. Dust samples were collected by using vacuum cleaners with sampling nozzles (ALK, Hørsholm, Denmark) on 10 nonencased mattresses of the Children's Hospital Santa Maria, Oberjoch, to control for exposure to the house dust mite (HDM) allergens Der p 1 and Der f 1. Dust collection was performed at 2 time points during the study period (December 2003 and August 2004) and subsequently analyzed for allergen content with a 2-sided mAb ELISA (Indoor Biotechnologies, Cardiff, United Kingdom). The mean concentration measured was 202 ng/g for Der p 1 and 435 ng/g for Der f 1, respectively (B. Eberlein et al, unpublished data, August 2007). These results show that HDM allergens are present in low concentrations at the study's altitude. Recruitment and inpatient rehabilitation were performed year round, with patient admissions from January 2003 until December 2004, omitting the possibility that the results observed were due to the avoidance of pollen exposure during the season. Temperature and relative humidity monitored throughout the study revealed values between 18°C and 27°C and 30% and 48%, respectively.Concerning the remarks of Piacentini et al,1Piacentini G.L. Peroni D.G. Bodini A. Boner A.L. Exhaled nitric oxide in asthmatic children at high altitude.J Allergy Clin Immunol. 2007; 120: 1226-1227Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar we agree that the residual HDM exposure in our study might account for the relatively smaller reduction of fractional exhaled nitric oxide (FeNO) from baseline compared with that seen in their investigation.3Piacentini G.L. Bodini A. Costella S. Vicentini L. Peroni D. Zanolla L. et al.Allergen avoidance is associated with a fall in exhaled nitric oxide in asthmatic children.J Allergy Clin Immunol. 1999; 104: 1323-1324Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar On the other hand, physiologic factors taking place at high altitude and reducing FeNO, such as increased hemoglobin concentration and hypoxia, are more pronounced at an altitude of 1750 m than at 1200 m,4Hahn A.G. Gore C.J. Martin D.T. Ashenden M.J. Roberts A.D. Logan P.A. An evaluation of the concept of living at moderate altitude and training at sea level.Comp Biochem Physiol. 2001; 128: 777-789Crossref Scopus (59) Google Scholar, 5Brown D.E. Beall C.M. Strohl K.P. Mills P.S. Exhaled nitric oxide decreases upon exposure to high-altitude hypoxia.Am J Hum Biol. 2006; 18: 196-202Crossref PubMed Scopus (37) Google Scholar, 6Le Cras T.D. McMurtry I. Nitric oxide production in the hypoxic lung.Am J Physiol Lung Cell Mol Physiol. 2001; 280: 575-582Google Scholar leading to a possible bias in the study by Piacentini et al,3Piacentini G.L. Bodini A. Costella S. Vicentini L. Peroni D. Zanolla L. et al.Allergen avoidance is associated with a fall in exhaled nitric oxide in asthmatic children.J Allergy Clin Immunol. 1999; 104: 1323-1324Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar which was not taken into consideration when data analysis was performed. In our study a significant FeNO reduction in the overall inpatient population independent of HDM sensitization was detected. Therefore in addition to HDM allergen avoidance, other factors might exist that are involved in the favorable effects of inpatient rehabilitation in the alpine climate on lung inflammation in asthmatic children. This hypothesis is further strengthened by a study carried out in Davos, Switzerland,7Karagiannidis C. Hense G. Rueckert B. Mantel P.Y. Ichers B. Blaser K. et al.High-altitude climate therapy reduces local airway inflammation and modulates lymphocyte activation.Scand J Immunol. 2006; 63: 304-310Crossref PubMed Scopus (55) Google Scholar at 1600 m of altitude, in which a significant reduction of FeNO compared with the baseline value was found after rehabilitation of patients with moderate allergic asthma (29.66 ppb, P < .01, n = 24), moderate intrinsic asthma (12.17 ppb, P < .05, n = 10), severe allergic asthma (37.53 ppb, P < .01, n = 25), and severe intrinsic asthma (53.39 ppb, P < .01, n = 13). As possible explanations of these findings, the design of the rehabilitation program and the absence of environmental pollutants have to be considered because allergen avoidance is of little value in intrinsic asthma.In our study the rehabilitation program included, among other items, physical exercise, a structured asthma education program, and, if necessary, supervised medical treatment. Concerning environmental pollution, no major sources are located in the proximity of the hospital, and recent ambient air measurements carried out by the Bavarian Environmental Agency showed only low mean concentrations of the following substances: carbon monoxide, 0.3 mg/m3; nitric oxide, 5 μg/m3; nitrogen dioxide, 14 μg/m3; benzene, 0.4 μg/m3; toluene, 1.2 μg/m3; and ultrafine particles PM10, 9.0 μg/m3, and PM2.5, 8 μg/m3 (mean values of measurements from October 5 to November 6, 2006).Our results indicate that at an altitude of 1200 m above sea level, effective rehabilitation programs can be offered, even with a small residual level of HDM exposure. We agree with Piacentini et al1Piacentini G.L. Peroni D.G. Bodini A. Boner A.L. Exhaled nitric oxide in asthmatic children at high altitude.J Allergy Clin Immunol. 2007; 120: 1226-1227Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar that HDM avoidance is only one of the beneficial factors of a high-altitude rehabilitation program, and therefore future research should aim to identify other factors involved in favorable health effects in asthmatic patients in the alpine setting. To the Editor: To address the issues Piacentini et al1Piacentini G.L. Peroni D.G. Bodini A. Boner A.L. Exhaled nitric oxide in asthmatic children at high altitude.J Allergy Clin Immunol. 2007; 120: 1226-1227Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar have raised, we are supplying additional data regarding our trial,2Huss-Marp J. Krämer U. Eberlein B. Pfab F. Ring J. Behrendt H. et al.Reduced exhaled nitric oxide values in children with asthma after inpatient rehabilitation at high altitude.J Allergy Clin Immunol. 2007; 120: 471-472Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar which were not included in the original publication because of space limitations. Dust samples were collected by using vacuum cleaners with sampling nozzles (ALK, Hørsholm, Denmark) on 10 nonencased mattresses of the Children's Hospital Santa Maria, Oberjoch, to control for exposure to the house dust mite (HDM) allergens Der p 1 and Der f 1. Dust collection was performed at 2 time points during the study period (December 2003 and August 2004) and subsequently analyzed for allergen content with a 2-sided mAb ELISA (Indoor Biotechnologies, Cardiff, United Kingdom). The mean concentration measured was 202 ng/g for Der p 1 and 435 ng/g for Der f 1, respectively (B. Eberlein et al, unpublished data, August 2007). These results show that HDM allergens are present in low concentrations at the study's altitude. Recruitment and inpatient rehabilitation were performed year round, with patient admissions from January 2003 until December 2004, omitting the possibility that the results observed were due to the avoidance of pollen exposure during the season. Temperature and relative humidity monitored throughout the study revealed values between 18°C and 27°C and 30% and 48%, respectively. Concerning the remarks of Piacentini et al,1Piacentini G.L. Peroni D.G. Bodini A. Boner A.L. Exhaled nitric oxide in asthmatic children at high altitude.J Allergy Clin Immunol. 2007; 120: 1226-1227Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar we agree that the residual HDM exposure in our study might account for the relatively smaller reduction of fractional exhaled nitric oxide (FeNO) from baseline compared with that seen in their investigation.3Piacentini G.L. Bodini A. Costella S. Vicentini L. Peroni D. Zanolla L. et al.Allergen avoidance is associated with a fall in exhaled nitric oxide in asthmatic children.J Allergy Clin Immunol. 1999; 104: 1323-1324Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar On the other hand, physiologic factors taking place at high altitude and reducing FeNO, such as increased hemoglobin concentration and hypoxia, are more pronounced at an altitude of 1750 m than at 1200 m,4Hahn A.G. Gore C.J. Martin D.T. Ashenden M.J. Roberts A.D. Logan P.A. An evaluation of the concept of living at moderate altitude and training at sea level.Comp Biochem Physiol. 2001; 128: 777-789Crossref Scopus (59) Google Scholar, 5Brown D.E. Beall C.M. Strohl K.P. Mills P.S. Exhaled nitric oxide decreases upon exposure to high-altitude hypoxia.Am J Hum Biol. 2006; 18: 196-202Crossref PubMed Scopus (37) Google Scholar, 6Le Cras T.D. McMurtry I. Nitric oxide production in the hypoxic lung.Am J Physiol Lung Cell Mol Physiol. 2001; 280: 575-582Google Scholar leading to a possible bias in the study by Piacentini et al,3Piacentini G.L. Bodini A. Costella S. Vicentini L. Peroni D. Zanolla L. et al.Allergen avoidance is associated with a fall in exhaled nitric oxide in asthmatic children.J Allergy Clin Immunol. 1999; 104: 1323-1324Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar which was not taken into consideration when data analysis was performed. In our study a significant FeNO reduction in the overall inpatient population independent of HDM sensitization was detected. Therefore in addition to HDM allergen avoidance, other factors might exist that are involved in the favorable effects of inpatient rehabilitation in the alpine climate on lung inflammation in asthmatic children. This hypothesis is further strengthened by a study carried out in Davos, Switzerland,7Karagiannidis C. Hense G. Rueckert B. Mantel P.Y. Ichers B. Blaser K. et al.High-altitude climate therapy reduces local airway inflammation and modulates lymphocyte activation.Scand J Immunol. 2006; 63: 304-310Crossref PubMed Scopus (55) Google Scholar at 1600 m of altitude, in which a significant reduction of FeNO compared with the baseline value was found after rehabilitation of patients with moderate allergic asthma (29.66 ppb, P < .01, n = 24), moderate intrinsic asthma (12.17 ppb, P < .05, n = 10), severe allergic asthma (37.53 ppb, P < .01, n = 25), and severe intrinsic asthma (53.39 ppb, P < .01, n = 13). As possible explanations of these findings, the design of the rehabilitation program and the absence of environmental pollutants have to be considered because allergen avoidance is of little value in intrinsic asthma. In our study the rehabilitation program included, among other items, physical exercise, a structured asthma education program, and, if necessary, supervised medical treatment. Concerning environmental pollution, no major sources are located in the proximity of the hospital, and recent ambient air measurements carried out by the Bavarian Environmental Agency showed only low mean concentrations of the following substances: carbon monoxide, 0.3 mg/m3; nitric oxide, 5 μg/m3; nitrogen dioxide, 14 μg/m3; benzene, 0.4 μg/m3; toluene, 1.2 μg/m3; and ultrafine particles PM10, 9.0 μg/m3, and PM2.5, 8 μg/m3 (mean values of measurements from October 5 to November 6, 2006). Our results indicate that at an altitude of 1200 m above sea level, effective rehabilitation programs can be offered, even with a small residual level of HDM exposure. We agree with Piacentini et al1Piacentini G.L. Peroni D.G. Bodini A. Boner A.L. Exhaled nitric oxide in asthmatic children at high altitude.J Allergy Clin Immunol. 2007; 120: 1226-1227Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar that HDM avoidance is only one of the beneficial factors of a high-altitude rehabilitation program, and therefore future research should aim to identify other factors involved in favorable health effects in asthmatic patients in the alpine setting.