A Short-Term Investigation of Dysphonia in Asthmatic Patients Using Inhaled Budesonide

A Short-Term Investigation of Dysphonia in Asthmatic Patients Using Inhaled Budesonide *,†Han Su Kim, ‡Jin Wook Moon, *,†Sung Min Chung, and §Ja Hyun Lee, *yzxSeoul, Korea Summary: Background. Dysphonia is one of the most common side effects of patients who use corticosteroid inhalers. The aim of this study was to investigate, prospectively, the occurrence of dysphonia in patients who used corticosteroid inhalers. Methods. Outpatients aged 18 years or older initially treated with inhaled corticosteroids were recruited. All patients were prescribed budesonide/formoterol. Questionnaires, perceptual studies, and acoustic analysis were performed five times during the study: at study entry and after 1, 4, 8, and 12 weeks. Videostroboscopy was performed at study entry and at 12 weeks. The data collected were analyzed by repeated-measures analysis of variance tests and Wilcoxon’s signed rank test (P < 0.01). Results. Sixty-two patients were enrolled and 29 patients (M:F ¼ 19:10) completed the study. Seven patients reported that they had problems with their voice; however, there were no statistically significant changes in the perceptual studies or the acoustic analysis. The videostroboscopy showed that ‘‘injection’’ and ‘‘increase of mucus’’ significantly increased by week 12. Vocal fold bowing was not noted in any of the patients. Conclusions. The results of this study showed no significant voice changes in patients using corticosteroid inhalers over a period of 3 months. However, minor mucosal changes were found on videostroboscopy. Key Words: Asthma–Steroid–Inhalation spacers–Voice.

INTRODUCTION Inhaled corticosteroid treatment has become standard care for patients with bronchial asthma.1 The most common local adverse effects of inhaled corticosteroid therapy have been reported to be candidiasis and dyphonia.2 Candidiasis rarely causes major clinical problems, and can usually be treated effectively without discontinuing inhaled corticosteroid. However, in patients with dysphonia, if it is severe, the only remedy is discontinuation of the inhaled corticosteroid treatment.2 The frequency of dysphonia with corticosteroid treatment has been reported to vary from 8% to 58%.3 The causes of dysphonia have not been fully determined. Many studies on the subject have not been reported by voice specialists but rather by respiratory physicians.2,4 In addition, the number of subjects studied has usually been small.5,6 Furthermore, the subjects included in most studies were patients who already complained of dysphonia.3,5,6 Moreover, most of the prior studies were retrospective and primitive acoustic analysis, with/without stroboscopic examination.3–5,7 Dysphonia is a highly subjective symptom, and variable factors (eg, smoking, laryngopharyngeal reflux disease [LPRD], and voice abuse history) are associated with the development of dysphonia. Therefore, objective investigation methods are needed for evaluation as well as specific and systematic incluAccepted for publication July 8, 2009. Conflict of interest: Dr. Kim, Dr. Moon, Dr. Chung, and Dr. Lee have no conflicts of interest to disclose. From the *Department of Otolaryngology, Ewha Womans University School of Medicine, Seoul, Korea; yEwha Medical Research Institute, Ewha Womans University School of Medicine, Seoul, Korea; zDepartment of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; and the xDepartment of Otolaryngology, Yonsei University College of Medicine, Seoul, Korea. Address correspondence and reprint requests to Han Su Kim, 911-1 MokDong, YangCheon-Gu, Ewha MokDong Hospital, Seoul, Korea. E-mail: [email protected] Journal of Voice, Vol. 25, No. 1, pp. 88-93 0892-1997/$36.00 Ó 2011 The Voice Foundation doi:10.1016/j.jvoice.2009.07.003

sion/exclusion criteria. The aim of this study was to investigate the occurrence of dysphonia in patients using inhaled corticosteroids with a prospective controlled study design.

MATERIALS AND METHODS Subjects Outpatients aged 18 years or older initially treated with an inhaled corticosteroid were recruited for the study. All patients were diagnosed with asthma in the department of pulmonology; they were prescribed budesonide/formoterol (Symbicort turbuhaler; AstraZeneka, Seoul, Korea) 160/4.5 mg twice per day. Patients were excluded if they had any prior asthma treatment or symptoms related to voice quality. Smokers and persons using their voice for their profession (eg, teachers, singers, and salesman) were also excluded. All patients were asked to fill out the reflux symptom index questionnaire (RSI)8 and had videostroboscopy performed to determine their reflux finding score (RFS).9 The patients who had an RSI and RFS that indicated laryngopharyngeal reflux disease were also excluded. None of the patients had a prior known history of laryngeal pathology or surgery on the larynx. A videostroboscopy was performed on all patients as part of their routine laryngeal examination at study entry. If any mucosal lesions, such as a vocal polyp/nodules, sulcus vocalis, leukoplakia, or vascular lesions, were found on examination, the patient was excluded from the study. The study was approved by the Institutional Review Board, and written informed consent was obtained from all patients. Methods All patients were assessed by perceptual studies and acoustic analysis on five occasions during the study: at study entry and after 1, 4, 8, and 12 weeks (visit 1, 2, 3, 4, and 5, respectively).

Han Su Kim, et al

The videostroboscopy was performed at study entry and at 12 weeks. Perceptual study. A reading of an approximately 1 minute and 20 second long sentence, from ‘‘San-Chak’’ (A walk), was recorded using the Lx Speech studio program (Laryngograph Ltd., London, UK). These readings were analyzed by a voice specialist. The ‘‘G’’ division of the Grade, Roughness, Asthenic, Breathiness, Strain (GRABS) scale was used to evaluate the recordings. The evaluation scale was from 0 to 3 using a 4-point rating scale (norm: 0; mild: 1; moderate: 2; and severe: 3). Acoustic analysis. Readings recorded into the Lx Speech studio were analyzed. The SPEAD (Speech Pattern Element Acquisition and Display; Laryngograph Ltd., London, UK) program was used for the analysis of the following parameters: the voice range profile 80%, the frequency distribution (Dfx), the amplitude quotient distribution (DAx), and the closed quotient distribution (DQx). Videostroboscopy. All patients were assessed by videostroboscopy (LxStrobe 3; Layngograph Ltd., London, UK). Three aspects—mucosal lesions, surface changes, and glottal closure—were evaluated (Table 1). Questionnaire. All patients were asked to complete a questionnaire at every visit. The questions were, ‘‘Do you think there is a problem with your voice?’’ and ‘‘ Do you have a sore throat?’’ The self-evaluation scale was from 0 to 3 using a 4-point rating scale (normal: 0; mild: 1; moderate: 2; and severe: 3). Statistics. Repeated-measures analysis of variance was used to compare the data from the perceptual study, the acoustic analysis, and the questionnaire, using a confidence level of 99% (SPSS version 11.5; SPSS Inc., Chicago, IL). The results of the videostroboscopy were analyzed with the Wilcoxon’s signed rank test, using a confidence level of 99%. RESULTS Sixty-two patients were enrolled in this study. Twenty-nine patients (M:F ¼ 19:10) completed the study. The mean age of the men was 46 years (range: 22–64 years) and that of the

TABLE 1. Scoring System for the Videostroboscopy Mucosal Lesion (Nodule/Polyp) Surface change Mucosal wave

None 0

Yes 2

Increasing of mucus

Normal 0 None 0 Normal 0

Decrease 1 Mild 1 Mild 1

None 2 Severe 2 Severe 2

Glottic closure

Complete

Mild bowing 1

Incomplete

Injection

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0

2

women was 33.4 years (range: 18–51 years). Seventeen patients were lost to follow-up. Thirteen patients were dropped from the study because of poor drug compliance or self-directed discontinuation of the steroid inhaler. Three patients were diagnosed with other diseases during the study period, and received additional medications (antibiotics, nonsteroidal anti-inflammatory drug [NSAID], and mucolytics), and hence, were excluded. The results of the perceptual studies were normal (grade ¼ 0) in 25 patients after 12 weeks. An increase in the GRABS scale was noted in four patients (13.7%, patient numbers 2, 5, 23, and 28). Seven patients (patient numbers 2, 4, 11, 15, 22, 24, and 25) answered that they had problems with their voice. Fifty-one percent of the patients reported a sore throat at least one or more times during the study period. There was no statistically significant change in the results of the questionnaires over the course of the study (Table 2). The measures of DFx, vocal range 80%, DQx, and DAx remained constant over the course of the study. In addition, there were no statistically significant changes in the acoustic analysis (Figures 1–4). TABLE 2. The Results of the GRABS Scale and Questionnaires Patient Number

Questionnaires*

Age

GRABS Scale*

Voice

Sore Throat

Male 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

22 64 52 64 60 49 47 50 62 53 59 53 45 35 35 24 30 23 47

0-0-0-0-0 1-1-1-2-2 0-0-0-0-0 0-0-0-0-0 1-1-1-1-1 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0

0-0-0-0-0 0-1-1-1-1 0-0-0-0-0 0-0-0-1-1 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-1-1-0-1 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-1-1-1-1 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0

0-0-0-0-0 0-1-1-1-1 0-0-0-1-1 0-0-0-1-2 0-1-1-1-2 0-0-0-0-0 0-0-2-1-1 0-0-0-0-0 0-0-1-1-1 0-0-0-0-0 0-1-1-1-1 0-1-0-0-0 0-0-0-0-0 0-1-1-0-1 0-1-0-0-1 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0

Female 20 21 22 23 24 25 26 27 28 29

37 34 23 28 50 51 32 35 18 26

0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-2-1-1-1 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 1-1-1-1-1 0-0-0-0-0

0-0-0-0-0 0-0-0-0-0 0-2-2-2-1 0-0-0-0-0 0-0-0-0-1 1-2-2-1-1 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-0

0-0-0-0-0 0-0-0-0-0 0-1-2-2-2 0-0-0-0-1 0-0-0-0-0 0-1-2-2-2 0-1-0-0-0 0-0-0-0-0 0-0-0-0-0 0-0-0-0-2

* The values mean the results of visits 1, 2, 3, 4, and 5, respectively. Norm: 0; mild: 1; moderate: 2; and severe: 3.

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FIGURE 1. The frequency distribution (Hz). The videostroboscopy exam showed that the scores for ‘‘injection’’ and ‘‘increase of mucus’’ were significantly increased at 12 weeks. The ‘‘injection’’ score increased from 0.34 ± 0.48 to 1.00 ± 0.80. A threefold increase of the score was also noted for mucus formation. A decrease in the mucosal wave was noted in only one patient (patient number 2), at both study entry and week 12. A mild degree of bowing of the true vocal fold was noted in three men and one woman (patient numbers 2, 5, 9, and 25, respectively) at study entry; however, there was no aggravation noted at the week 12 examination. Mucosal lesions, such as polyps/nodules, were not found in any of the patients (Table 3). DISCUSSION Many clinicians have the impression that corticosteroid inhalers are associated with voice problems. However, there is no systematic data, collected to date, to support this concern. The frequency of dysphonia has been reported in 8–58% of the patients treated with inhaled corticosteroids.3 In the present study, dysphonia was reported in 24% of the patients, based on the results of the self-report questionnaires. However, we did not find any deterioration of the voice after the use of steroid inhalers by objective measures, including the GRABS scale and the acoustic analysis. The different findings from our study compared with prior studies might be explained by the following. First, our study entry criteria were different from prior investigations. The subject groups from most previous studies included patients who complained of dysphonia after beginning treatment with a steroid inhaler; however, in our study, we included patients who started using the steroid inhaler without any voice-related

symptoms. We also excluded patients who smoked and used their voice professionally as well as those who had signs of laryngopharyngeal reflex (LPRD). Prior reports have demonstrated a close correlation between LPRD and dysphonia.10 In addition, acoustic parameters have been shown to improve after treating the LPRD.11 We thought it important to exclude patients suspected of having LPRD when investigating the quality of the voice. Second, this study has short study duration and the sample size is small. Dysphonia could develop after 3 months using inhaled corticosteroids.2,5 If the study period were longer than 3 months, the results showed different outcomes. Sixty-two patients had been initially enrolled and only 29 patients finished the study. Thirty-three patients failed to complete the study. Half of them (17 patients) forgot the visiting time and did not perform the scheduled examination. The reasons why they could not finish the study are not completely understood; poor drug compliance with dysphonia or sore throat could be one of the reasons. The number 29 is too small to generalize the results of our study as a fact. Several previous studies suggested that inhaled corticosteroid-induced dysphonia is caused by myopathic bowing of the vocal folds.2,5 Williams et al examined asthmatic patients with dysphonia, who were treated with inhaled corticosteroids, and identified what they characterized as ‘‘a characteristic abnormality’’; that is, bowing of the vocal folds, in nine out of 14 patients.5 They postulated that this bowing was the result of a bilateral adductor myopathy induced by local deposition of topical steroids.5 However, their results can be questioned. First, they used mirror laryngoscopy and fiberoptic laryngoscopy for their evaluations. These investigation tools have

FIGURE 2. The voice range profile 80%.

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FIGURE 3. The closed quotient distribution (%). a low-resolution power and cannot evaluate the fine movement and closure of the vocal fold. Second, the mean age of the patients studied, with adductor myopathy, was 62 years, whereas that of the normal group was 51 years. The ‘‘bowing’’ of the vocal folds is a common feature that develops during aging; it is thought to be the result of atrophy of the laryngeal musculature. A prior study has documented a correlation between changes in muscular function and voice parameters in older individuals.12 Therefore, the findings of bowing of the vocal folds in the study reports by Williams might be interpreted as being the result of the normal aging process. The age of four of our patients, with bowing of the true vocal fold by videostroboscopy, was higher than the mean age of the other subjects. (They were 64, 60, 62, and 51.) Third, six of the nine patients with bowing of the vocal folds complained of dysphonia within 4 weeks after starting steroid inhaler treatment; this is too short a time for a bilateral adductor myopathy to be caused by local deposition of topical steroids. In our study, there was no aggravation or newly developed bowing lesions at the 12th-week videostroboscopy. The results of DQx do not indicate any significant glottal insufficiency. Although we did not find bowing of the vocal folds, the videostroboscopy results were suggestive of vocal fold irritation. The scores for ‘‘injection’’ and ‘‘increase of mucus’’ were significantly increased at week 12. Asthma patients using a corticosteroid inhaler may be at a greater risk for laryngeal microtrauma because of the lower inspiratory flow rates, and a greater chance for particle deposition in the larynx.13 The turbulent airflow of the corticosteroid inhaler, at the level of the vocal folds, especially at the glottic margin, can lead to

mucosal injury and the development of enlarged blood vessels, varices, and small hemorrhages.6 In our study, 66% (eight patients with a severe degree and 11 patients with a mild degree) showed increase in the mucosal injection at the week 12 examination. However, there were no mass-like lesions (polyps/nodules). Dysphonia might be related to mucus preventing the closure of the glottis.3 It is possible that these minor mucosal changes could cause dysphonia, even though the acoustic analysis did not detect the changes. An increase in the results from the GRABS scale was noted in four patients during the entire study period. Two patients (patient numbers 5 and 28) had ‘‘grade 1 hoarseness’’ from the first visit to the last visit without deterioration and one patient (patient number 23) had ‘‘grade 1 hoarseness’’ at only the second-visit examination (week 1). Therefore, there was only one patient (patient number 2) who showed increase on the GRABS scale after using the steroid inhaler among 29 patients (3.4%). This patient was a 64-year-old man; he complained of hoarseness at the second visit, and the grade of the ‘‘G’’ was aggravated, from 1 to 2, at the fourth visit. However, there was no significant change in the results of the acoustic analysis. The mean speaking fundamental frequency of the patient ranged from 187.69 to 193.19 Hz, higher than that of a normal adult male. This patient also showed an increase in the mucosal wave on videostroboscopy. We supposed that the patient used a falsetto phonation, and was suffering from presbyphonia. The hoarseness was characteristic of the falsetto and presbyphonia. A significant proportion of the patients (51%) in this study complained of a sore throat. However, 24% (7 of 29) of the patients reported problems with their voice. All patients with

FIGURE 4. The amplitude quotient distribution (dB).

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TABLE 3. The Results of the Videostroboscopy At Entry/Week 12 Surface Changes Patient Number

Mucosal Lesion

Wave

Injection

Mucus

Glottic Closure

Total

Male 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Mean ± SD (male)

0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0

0/0 1/1 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0.05 ± 0.23/ 0.05 ± 0.23

0/0 1/2 0/0 0/1 1/2 1/2 0/1 0/0 1/1 0/1 1/2 1/1 0/1 0/1 0/2 0/1 0/0 1/2 0/0 0.37 ± 0.05/ 1.05 ± 0.78*

0/0 1/2 0/1 0/1 1/1 0/1 0/2 0/0 1/1 0/1 1/1 0/0 0/1 1/1 0/1 0/1 0/0 0/1 1/1 0.32 ± 0.48/ 0.89 ± 0.57*

0/0 1/1 0/0 0/0 1/1 0/0 0/0 0/0 1/1 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0.16 ± 0.37/ 0.16 ± 0.17

0/0 4/6 0/1 0/2 3/4 1/3 0/3 0/0 3/3 0/2 2/3 1/1 0/2 1/2 0/3 0/2 0/0 1/3 1/1 0.89 ± 1.24/ 2.16 ± 1.50*

Female 20 21 22 23 24 25 26 27 28 29 Mean ± SD (female)

0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0

0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0

Mean ± SD (total)

0/0

0.03 ± 0.19/ 0.03 ± 0.19

0/0 1/2 0/0 0/0 0/2 1/2 1/1 0/1 0/0 0/1 0.3 ± 0.48/ 0.9 ± 0.88* 0.34 ± 0.48/ 1.00 ± 0.80*

0/0 0/1 0/0 0/0 0/1 1/1 0/0 0/1 0/0 0/0 0.1 ± 0.32/ 0.4 ± 0.52* 0.24 ± 0.44/ 0.72 ± 0.59*

0/0 0/0 0/0 0/0 0/0 1/1 0/0 0/0 0/0 0/0 0.1 ± 0.32/ 0.1 ± 0.32 0.14 ± 0.35/ 0.15 ± 0.35

0/0 1/3 0/0 0/0 0/3 3/4 1/1 0/2 0/0 0/1 05 ± 0.97/ 1.4 ± 1.51* 0.76 ± 1.15/ 1.90 ± 1.52*

Abbreviation: SD, standard deviation. * P < 0.01.

dysphonia, except one patient (patient number 24, a 50-year-old female patient, who answered that she had a mild voice problem, only one time at the fifth visit), also had a sore throat. Two patients (patient numbers 22 and 25) complained of a similar degree of dysphonia and sore throat. Perhaps, a sore throat could make one feel like there is a problem with one’s voice subjectively, even though there were no objective problems noted; the results of a previous study supports this supposition.14 We performed KOH mountain for detecting the candida infection in the patients complaining of sore throat. All of the results were negative. We did not find out the cause of sore

throat, but corticosteroid inhaler may induce the irritation around the upper airway mucosa. Another important consideration for understanding the quality of voice production is the impact of the asthma itself. The airflow from the lungs and the mucosal vibration at the glottis are the two key components of voice production. The underlying reduced pulmonary reserve associated with asthma may therefore significantly impact the quality of the voice. Lee et al measured speech segment durations of various lengths in asthmatics compared with healthy controls, and found that the asthmatics had various abnormalities, including increased

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Dysphonia in Asthmatic Patients

pause time between speech segments, fewer syllables per breath, and a larger percentage of time spent in nonspeech ventilatory activity.15 In a recent study involving children, an age-matched control group with asthma that never received exogenous corticosteroids, had a 20% rate of dysphonia.16 Other studies have reported that the vocal function improved with inhaled corticosteroid.4,17 Dysphonia has been reported to occur in 30–50% of patients treated with an inhaled corticosteroid administered by a pressurized metered dose inhaler. However, the frequency of dysphonia has been reported to be reduced in patients using a dry powder device.7 Therefore, in the present study, all patients were treated with the Symbicort turbuhaler, a dry powder device. However, it remains to be proven whether there is a difference between the two devices with regard to their effect on the voice quality.2 CONCLUSION The presence of dysphonia in patients using a corticosteroid inhaler was investigated prospectively using objective measurements. There were no significant changes associated with dysphonia in the perceptual studies or on the acoustic analysis during 3 months’ study period. Vocal fold bowing and atrophy of the vocalis muscle was not found; however, minor mucosal changes, including injection of the vocal fold and increased mucus formation, were noted by videostroboscopy. REFERENCES 1. Tse CS, Bernstein IL. Corticosteroid aerosols in the treatment of asthma. Pharmacotherapy. 1984;4:334–342. 2. Crompton GK, Sanderson R, Dewar MH, et al. Comparison of Pulmicort pMDI plus Nebuhaler and Pulmicort Turbuhaler in asthmatic patients with dysphonia. Respir Med. 2000;94:448–453.

93 3. Lavy JA, Wood G, Rubin JS, et al. Dysphonia associated with inhaled steroids. J Voice. 2000;14:581–588. 4. Balter MS, Adams SG, Chapman KR. Inhaled beclomethasone dipropionate improves acoustic measures of voice in patients with asthma. Chest. 2001;120:1829–1834. 5. Williams AJ, Baghat MS, Stableforth DE, et al. Dysphonia caused by inhaled steroids: recognition of a characteristic laryngeal abnormality. Thorax. 1983;38:813–821. 6. Mirza N, Kasper Schwartz S, Antin-Ozerkis D. Laryngeal findings in users of combination corticosteroid and bronchodilator therapy. Laryngoscope. 2004;114:1566–1569. 7. Engel T, Heinig JH, Malling HJ, et al. Clinical comparison of inhaled budesonide delivered either via pressurized metered dose inhaler or Turbuhaler. Allergy. 1989;44:220–225. 8. Belafsky PC, Postma GN, Koufman JA. Validity and reliability of the reflux symptom index (RSI). J Voice. 2002;16:274–277. 9. Belafsky PC, Postma GN, Koufman JA. The validity and reliability of the reflux finding score (RFS). Laryngoscope. 2001;111:1313–1317. 10. Cesari U, Galli J, Ricciardiello F, et al. Dysphonia and laryngopharyngeal reflux. Acta Otorhinolaryngol Ital. 2004;24:13–19. 11. Jin J, Lee YS, Jeong SW, et al. Change of acoustic parameters before and after treatment in laryngopharyngeal reflux patients. Laryngoscope. 2008;118:938–941. 12. Kendall K. Presbyphonia: a review. Curr Opin Otolaryngol Head Neck Surg. 2007;15:137–140. 13. Grant D. A caution in the use of laryngeal sprays. 1898. J Laryngol Otol. 1998;112:506. 14. Williamson IJ, Matusiewicz SP, Brown PH, et al. Frequency of voice problems and cough in patients using pressurized aerosol inhaled steroid preparations. Eur Respir J. 1995;8:590–592. 15. Lee L, Chamberlain LG, Loudon RG, et al. Speech segment durations produced by healthy and asthmatic subjects. J Speech Hear Disord. 1988;53:186–193. 16. Agertoft L, Larsen FE, Pedersen S. Posterior subcapsular cataracts, bruises and hoarseness in children with asthma receiving long-term treatment with inhaled budesonide. Eur Respir J. 1998;12:130–135. 17. Watkin KL, Ewanowski SJ. Effects of aerosol corticosteroids on the voice: triamcinolone acetonide and beclomethasone dipropionate. J Speech Hear Res. 1985;28:301–304.