Safety and efficacy of warfarin in patients with moderate thrombocytopenia.

INTRODUCTION: Patients with moderate thrombocytopenia and comorbidities requiring anticoagulation are currently sub-optimally treated because of bleeding concerns. Guidance on anticoagulating such patients is currently lacking because of limited data on safety and efficacy of anticoagulation in such patients. METHODS: This retrospective study compared the incidence of bleeding and thrombosis in a cohort of warfarinized patients with sustained platelet counts below 100×109/L against a cohort with normal platelet counts (>140×109/L). Primary outcomes of safety and efficacy were determined by incidence rate ratios (IRR) of bleeding and thrombotic events. International normalized ratio (INR) and platelet counts during adverse events in thrombocytopenic arm were secondary outcomes. RESULTS: 137 thrombocytopenic patients (104,985 patient-exposure days) were compared against 939 normal patients (715,193 patient-exposure days). IRR of minor, major bleeding and thrombosis among thrombocytopenic patients were 3.03 (95% CI: 1.57-5.60), 1.48 (95% CI: 0.44-3.98), and 0.807 (95% CI: 0.09-3.43) respectively. Median INR and platelet count readings during minor and major bleeds were 3.60 (IQR: 2.70-4.12) and 3.12 (IQR: 2.82-4.22), and 99×109/L (IQR: 77.0-147.0×109/L) and 115×109/L (IQR: 107.5-169.5×109/L) respectively. CONCLUSION: Warfarinized thrombocytopenic patients are at higher risk of minor bleeding complications with a higher tendency for major bleeding but derive similar benefits against thrombotic events compared to normal patients. Bleeding events are associated with higher INRs. A narrow INR target with an upper limit below 2.5 together with closer anticoagulation monitoring may improve safety of patients.

International consensus on (ICON) pediatric asthma.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

An acoustical respiratory phase segmentation algorithm using genetic approach.

This paper proposes a robust and fully automated respiratory phase segmentation method using single channel tracheal breath sounds (TBS) recordings of different types. The estimated number of respiratory segments in a TBS signal is firstly obtained based on noise estimation and nonlinear mapping. Respiratory phase boundaries are then located through the generations of multi-population genetic algorithm by introducing a new evaluation function based on sample entropy (SampEn) and a heterogeneity measure. The performance of the proposed method is analyzed for single channel TBS recordings of various types. An overall respiratory phase segmentation accuracy is found to be 12 +/- 5 ms for normal TBS and 21 +/- 9 ms for adventitious sounds. The results show the robustness and effectiveness of the proposed segmentation method. The proposed method has been a successful attempt to solve the clinical application challenge faced by the existing phase segmentation methods in terms of respiratory dysfunctions.

A filter bank-based source extraction algorithm for heart sound removal in respiratory sounds.

In this paper, we consider the problem of heart sounds (HS) removal from respiratory sounds (RS), and a novel semi-blind single-channel source extraction algorithm is proposed. The proposed method is able to extract the underlying pure RS from the HS corrupted noisy input signals by incorporating the filter banks and template-based matching using FIR filters. For performance evaluation of the presented method, the average power spectral densities (PSD) of the input RS segments without HS have been compared with the PSD of the reconstructed signals over six selected frequency bands from 20 to 800Hz. The proposed method is tested for various types of RS recordings and found effective by yielding an overall maximum spectral difference of 2.8707+/-0.9875dB for a frequency range below 800Hz.

Monitoring and treatment practices of childhood asthma in Singapore: a questionnaire study.

INTRODUCTION: Asthma is the most common chronic disease in children in Singapore. More than 20 percent of children will have been diagnosed with asthma by the age of 15 years. Most children are seen in the primary care setting, thus it is of value to study the management practices, especially of general practitioners, with comparison to gold standards. The aims of the study were to investigate: (a) Methods of monitoring asthma control; (b) Practices in managing acute exacerbations; and (c) Choice of therapy in maintenance treatment. METHODS: 2,100 questionnaires consisting of 35 questions were sent by post to general practitioners and various paediatric doctors throughout Singapore. 173 valid responses were received and results were compared to the 2006 Global Initiative for Asthma guidelines. RESULTS: 76.3 percent of respondents were general practitioners. 89.1 percent did not use symptom score cards / diaries. 37.6 percent did not use peak-flow meters / spirometers. 83.8 percent used a short-acting beta-agonist in acute exacerbations, but only 41.0 percent used oral corticosteroids in outpatients. A significant number used long-acting beta-agonists (LABA) in combination with inhaled steroids (29.5-41.6 percent) or as monotherapy (5.8-8.7 percent) for maintenance treatment. 91.3 percent never used immunotherapy in practice. CONCLUSION: Greater usage of diaries / score cards can be encouraged along with objective peak flow / spirometry measurements. Management of acute exacerbations is appropriate but corticosteroids are under-prescribed by most doctors. LABA continues to be prescribed for maintenance despite a lack of established safety profile for infants, along with recommendations that they only be used selectively in patients poorly-controlled by medium-dosage inhaled corticosteroids.

Acoustic rhinometry in nasal allergen challenge study: which dimensional measures are meaningful?

BACKGROUND: Acoustic rhinometry (AR) is commonly used as a quantitative assessment of nasal response to nasal allergen challenge (NAC). However, sources of error and physical limitations of various AR area-distance measurements have not been adequately evaluated. OBJECTIVE: To investigate the clinical value of AR measurements, and the relationship between subjective sensation and objective AR measurements in the NAC study. METHODS: Nasal challenge using increasing concentrations of crude Blomia tropicalis (Bt) extracts (0.6, 6, and 60 microg/mL) was performed in 15 adult patients (eight males and seven females) with ongoing persistent allergic rhinitis. Subjective symptom scores of nasal obstruction were recorded together with the objective AR measurements of the minimum cross-sectional area (MCA), distance to MCA and cross-sectional area (CSA) at 3.3, 4.0 and 6.4 cm from the nostril, during the 7 h after the last challenge. RESULTS: The dose-response increase in nasal obstruction score was significantly (P<0.001 for all) associated with decreases in mean MCA (r=0.75), mean CSA3.3 (r=0.54), mean CSA4.0 (r=0.53) and mean CSA6.4 (r=0.20). The mean MCA (+/-SD) for each subjective symptom score 0, 1, 2 and 3 was found to be 0.73 (+/-0.22) cm2, 0.63 (+/-0.29) cm2, 0.33 (+/-0.17) cm2 and 0.21 (+/-0.14) cm2, respectively. When the MCA (left and right separately) reached an area <0.2 cm2, measurements of CSA3.3 and CSA4.0 were significantly reduced by 60-70%. CONCLUSION: This study demonstrates that AR is a useful and objective investigational tool, which correlates well with the sensation of nasal obstruction. MCA, CSA3.3 and CSA4.0 are more reliable measurements than CSA6.4 due to physical limitations. It is important to note that when the MCA is smaller than 0.2 cm2, a common condition in the early-phase reaction, area-distance measurements beyond this point can be misinterpreted and should be considered with caution.

The prevalence of asthma and allergies in Singapore; data from two ISAAC surveys seven years apart.

BACKGROUND AND AIMS: Over the past few decades, the prevalence of asthma has been increasing in the industrialised world. Despite the suggestion of a similar increase in Singapore, the 12 month prevalence of wheeze among schoolchildren in 1994 was 2.5-fold less than that reported in western populations. It was hypothesised that with increasing affluence in Singapore, the asthma prevalence would further increase and approach Western figures. A second ISAAC survey was carried out seven years later to evaluate this hypothesis. METHODS: The cross-sectional data from two ISAAC questionnaire based surveys conducted in 1994 (n = 6238) and in 2001 (n = 9363) on two groups of schoolchildren aged 6-7 and 12-15 years were compared. The instruments used were identical and the procedures standardised in both surveys. RESULTS: Comparing data from both studies, the change in the prevalence of current wheeze occurred in opposing directions in both age groups--decreasing in the 6-7 year age group (16.6% to 10.2%) but increasing to a small extent in the 12-15 year age group (9.9% to 11.9%). The 12 month prevalence of rhinitis did not change; there was an increase in the current eczema symptoms in both age groups. CONCLUSION: The prevalence of current wheeze, a surrogate measure of asthma prevalence, has decreased significantly in the 6-7 year age group. Eczema was the only allergic disease that showed a modest increase in prevalence in both age groups.

Pulmonary function and scoliosis in children with spinal muscular atrophy types II and III.

AIMS: The objectives were to evaluate the clinical course of spinal muscular atrophy (SMA) types II and III patients necessitating scoliosis surgery at the National University Hospital, Singapore. METHODS: A retrospective review of SMA types II and III patients, born over a 10-year period between 1983 and 1992, was conducted. RESULTS: There were eight patients: four with SMA type II and four with SMA type III. The mean age at scoliosis surgery was 9 years 7 months (range 7 years 6 months-12 years 4 months). The mean preoperative Cobb angle was 65.4 degrees (range 43-90 degrees ) and the mean postoperative Cobb angle was 22.6 degrees (range 12-45 degrees ), with a mean correction of 64.8% (range 47.7-77.8%). The decline in percentage predicted forced vital capacity (FVC) was 7.7% (95% CI: 12.4% to 3.0%) per year preoperatively and this was reduced to 3.8% (95% CI: 5.8% to 1.9%) per year postoperatively. The mean length of preoperative and postoperative lung function follow-up was 6.3 months (range 0.03-31 months) and 44 months (range 0-110 months), respectively. CONCLUSIONS: This study suggests that pulmonary function in SMA types II and III continues to decline after scoliosis surgery, though the rate of decline is less marked. Overall, the combined results from this study and all other previously published studies are conflicting in regard to the effect of scoliosis surgery on pulmonary function in SMA types II and III, though half of the studies (3 of 6) did demonstrate a continued decline in lung function postoperatively. This decline in pulmonary function despite spinal stabilization is likely secondary to the progressive neuromuscular weakness of the disease.

The upper and lower airway responses to nasal challenge with house-dust mite Blomia tropicalis.

BACKGROUND: The house dust mite Blomia tropicalis (B. tropicalis) was found to be the most prevalent domestic mite in Singapore. However, its pathogenicity in allergic airway diseases remains to be investigated. METHODS: Twenty adults with persistent allergic rhinitis (PAR) were studied. Five had a history of asthma, and all were asymptomatic except one who was under treatment with low-dose inhaled corticosteroid. Nasal challenge was carried out by nasal spray with phosphate-buffered saline (PBS) and with increasing concentrations of crude B. tropicalis extracts (0.6, 6.0 and 60 micro g/ml) at 15 min intervals. Subjective symptom scores and absolute number of sneezes were recorded together with objective measurements of spirometry (forced expiratory volume in 1 s, FEV1) and acoustic rhinomanometry (volume of the nasal cavity). These were performed at baseline, 5 min after each incremental challenge, and 30 min, 1 h, 3 h, 5 h and 7 h after the last challenge. Meanwhile, concentrations of mediators in nasal secretions (tryptase, leukotriene C4 (LTC4) and eosinophil cationic protein (ECP)) were measured in nasal aspirate samples at similar time intervals. An identical (control) challenge procedure with PBS alone was repeated in seven patients after a washout period of at least 2 weeks. RESULTS: Significant increases in the subjective and objective nasal symptoms, together with a significant increase of tryptase and LTC4 concentrations in nasal secretion, were found 5 min after each challenge with B. tropicalis, but not with PBS. There was no definitive pattern of the late-phase nasal response in either subjective symptoms or objective measurements. Three patients (3/5) with a history of asthma showed a fall in FEV1 readings (33%, 22% and 11% from baseline, respectively) at 7 h post challenge with concomitant mild wheezing in the night. CONCLUSIONS: Our study demonstrates direct evidence of allergic nasal response to B. tropicalis in sensitized adults. It shows that nasal provocation may also provoke concomitant asthmatic symptoms during the late-phase reaction, especially in people with a history of asthma.

Sleep architecture and respiratory disturbances in children with obstructive sleep apnea.

Little is known regarding sleep architecture in children with the obstructive sleep apnea syndrome (OSAS). We hypothesized that sleep architecture was normal, and that apnea increased over the course of the night, in children with OSAS. We analyzed polysomnographic studies from 20 children with OSAS and 10 control subjects. Sleep architecture was similar between the groups. Of obstructive apneas 55% occurred during rapid eye movement (REM) sleep. The apnea index, apnea duration, and degree of desaturation were greater during REM than non-REM sleep. OSAS data from the first and third periods of the night (periods A and C) were compared. Both the overall and the REM apnea index increased between periods A and C (11 to 25/h, p < 0.02; and 24 to 51/h, p < 0.01, respectively). There was no difference in Sa(O(2)) over time. Spontaneous arousals, but not respiratory-related arousals, were more frequent during non-REM than REM sleep; these did not change from periods A to C. We conclude that children with OSAS have normal sleep stage distribution. OSAS is predominantly a REM phenomenon in children. Obstructive apnea worsens over the course of the night, independent of the changing amounts of REM sleep. We speculate that this increase in apnea severity may be secondary to upper airway muscle fatigue, changes in upper airway neuromotor control, or changes in REM density.

Evaluation of the allergenicity of tropical pollen and airborne spores in Singapore.

BACKGROUND: Sensitization to pollen and spores of the Southeast Asian tropical region is not well documented. This study evaluated the allergenicity of the tropical airspora in Singapore. METHODS: On the basis of the results of an aerobiologic survey of the airspora profile of Singapore, crude extracts of 23 main spore (fungal and fern) and pollen types were prepared. A total of 231 patients with asthma and/or allergic rhinitis and 76 healthy controls were evaluated by skin prick test (SPT). Total and specific IgE levels were also quantified by the fluorescence allergosorbent test (FAST). RESULTS: All 23 allergenic extracts tested elicited positive SPT responses. Among the patients with atopic diseases, extracts of oil-palm pollen (Elaeis guineensis) were observed to have the highest frequency of positive reactions (40%), followed by extracts of resam-fern spores (Dicranopteris linearis) (34%) and sea-teak pollen (Podocarpus polystachyus) (33.8%). Fungal spores with the highest SPT responses were Curvularia spp. (26-32%) and Drechslera-like spores (31%). Positive responses to these extracts correlated with total serum IgE levels of the subjects and were significantly associated with the presence of atopic disease. CONCLUSIONS: We have documented sensitization to tropical pollen and spores in our population. Its association with atopy suggests that it has a role in allergic diseases in the tropics.

Sensitization to local dust-mite fauna in Singapore.

BACKGROUND: Recent studies showed the presence of a unique dust-mite fauna in the indoor environment of Singapore. Immediate hypersensitivity to these dust mites, along with other known indoor allergens, may play a role in the pathogenesis of allergic respiratory diseases. This study evaluated the sensitization rates of the local atopic population to these allergens. METHODS: The skin prick test was performed on a total of 391 individuals (289 patients with asthma and/or allergic rhinitis and 102 healthy controls) using extracts of six species of local dust mites (Austroglycyphagus malaysiensis, Blomia tropicalis, Dermatophagoides pteronyssinus, D. farinae, Sturnophagoides brasiliensis, and Tyrophagus putrescentiae) and 10 other common indoor allergens. Total serum IgE and specific IgE to these dust mites were also quantified with the fluorescence allergosorbent test (FAST). RESULTS: The sensitization rates among patients with asthma and/or allergic rhinitis to dust mites and other inhalant allergens tested (via skin prick tests) were as follow: B. tropicalis (96.2%), D. pteronyssinus (93.4%), D. farinae (92.3%), A. malaysiensis (78.2%), S. brasiliensis (71.6%), T. putrescentiae (71.3%), canary feathers (69.9%), Periplaneta americana (cockroach) (59.5%), Blattella germanica (cockroach) (56.4%), mosquito (Aedes sp.) (46.4%), dog epithelia (mixed breed) (34.3%), kapok seed (31.8%), cat hair (29.1%), Aspergillus fumigatus (20.8%), Penicillium notatum (18.0%), and Candida (Monilia) albicans (9.3%). All patients were observed to react to at least three of the six dust-mite extracts, with 254/289 (87.9%) reacting to at least five or to all six. Skin prick responses to the dust mites were found to correlate with the corresponding specific IgE levels quantified by FAST (P<0.001). In addition, specific IgE levels to D. pteronyssinus and D. farinae were highly correlated (Spearman's rank coefficient = 0.76, P<0.001), as were those to B. tropicalis and A. malaysiensis (r = 0.60, P<0.001). CONCLUSIONS: Asthma and/or allergic rhinitis patients were highly sensitized to the local dust-mite fauna. Thus, these dust mites should be considered important allergenic sources of this region.

Under-recognition of childhood asthma in Singapore: evidence from a questionnaire survey.

In a recent study on the prevalence of childhood asthma and allergies using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires, 6238 Singapore school children in two age-groups, 6-7 years (n = 2030) and 12-15 years (n = 4208), were evaluated. Of the 1856 children who reported asthma-like symptoms (wheezing, exercise-wheezing, persistent nocturnal cough), 919 (49%) had not been diagnosed asthmatic. Of these undiagnosed children, 731 (39%) reported current symptoms of asthma. Under-recognition of asthma was more prevalent among those with persistent nocturnal cough and mild symptoms. In addition, the discordance between wheezing in the last 12 months and a diagnosis of asthma was significantly higher among the younger age-group (6-7 years), but exercise-induced wheezing was less recognized as a symptom of asthma among the older age-group (12-15 years). This study has shown that there is a substantial degree of under-recognition of asthma among school children in Singapore.

Unfused hypoplastic tongue in a newborn.

Malformations of the tongue are rare. There are < 50 cases of tongue hypoplasia reported in the literature since the first case described by de Jussieu in 1718. These are usually associated with the hypoglossia-hypodactaly syndrome. We describe a newborn with a hypoplastic anterior tongue unfused to the posterior tongue and airway obstruction. Its embryology, theories of pathogenesis, treatment and clinical course are discussed.

Association of ambient air-pollution levels with acute asthma exacerbation among children in Singapore.

BACKGROUND: Air-pollution levels have been shown to be associated with increased morbidity of respiratory diseases. METHODS: Data for ambient air-pollutant levels, meteorologic factors, and hospitalization or emergency room (ER) visits for acute asthma in Singapore children over a 5-year period (1990-4) were obtained and analyzed for associations by time-series methods. RESULTS: Throughout this period, the annual mean and 24-h mean levels for sulfur dioxide (SO2), nitrogen dioxide (NO2), and total suspended particles (TSP) and maximum 1-h daily average for ozone were generally within the air-quality guidelines established by the World Health Organization (WHO). However, positive correlation between levels of each of these pollutants and daily ER visits for asthma was observed in children aged 3-12 years, but not among adolescents and young adults (13-21 years old). The association with SO2 and TSP persisted after standardization for meteorologic and temporal variables. An adjusted increase in 2.9 ER visits for every 20 microg/m3 increase in atmospheric SO2 levels, lagged by 1 day, was observed on days when levels were above 68 microg/m3. With TSP, an adjusted increase of 5.80 ER visits for every 20 microg/m3 increase in its daily atmospheric levels, lagged by 1 day, was observed on days with levels above 73 microg/m3. Similar results were also obtained after controlling for autocorrelation by time-series analysis. CONCLUSIONS: These associations were observed even though the overall levels of all pollutants were generally within the air-quality guidelines established by the WHO. These findings suggest that asthmatic children are susceptible to increased levels of air pollutants, particularly SO2 and TSP, although the ambient levels are generally within "acceptable" ranges.

The economic cost of asthma in Singapore.

BACKGROUND: Asthma is a common chronic disorder. In Singapore, it is estimated that 140,000 individuals have current asthma and more than 100 individuals die of this disease annually. OBJECTIVE: This study estimates the economic cost of asthma, both direct and indirect, to the patient and community. METHOD: Direct cost estimates were based on all levels of medical care, which included inpatient care, emergency room visits, specialist outpatient and primary healthcare, and medication costs. Indirect costs were estimated from cost of time lost by patients and their families attending to medical needs and the loss of productivity due to absenteeism. These estimates were calculated to the 1992/93 US dollar. RESULTS: The total cost of asthma in Singapore was estimated to be US $33.93 million per annum. This was made up of US $17.22 million in direct costs and US $16.71 million in indirect costs. Inpatient hospitalisation accounted for the largest proportion of direct medical expenditure, approximately US $8.55 million. The loss of productivity from acute asthma accounted for the largest proportion of the indirect costs at US $12.70 million. The cost estimates did not include premature death due to disease. These estimates represent approximately US $238 per asthmatic person per year or US $11.90 per person per year. CONCLUSION: This study shows that the economic cost of asthma is also considerable in populations outside the Western hemisphere, and justifies the need for a concerted effort to reduce asthma morbidity worldwide.

Geographical comparison of the prevalence of childhood asthma and allergies in Singapore.

A previous study suggested that differences in the prevalence of respiratory illnesses such as asthma in school children in different regions of Singapore were not due to the influence of air pollution or environmental factors but possibly to cultural and socio-economic factors. The effects of socio-economic or demographic variables were, however, not shown in that study. In this study, we set out to discover whether regional differences in the prevalence of atopic diseases such as asthma, rhinitis and eczema in Singapore school children could be explained by different demographic profiles. The prevalence of asthma and allergies were evaluated in 6238 Singapore school children in two age groups (6-7 years [n = 2030] and 12-15 years [n = 4208]). They were from four regions, based on residential post codes. Demographic and socio-economic data were also obtained. The questionnaire of the International Study on Asthma and Allergies in Childhood (ISAAC) was used. The data showed that children residing in the northern regions of Singapore had a significantly lower prevalence of asthma and rhinitis than those in other regions. When controlled for demographic influences (age, sex and race) and socio-economic factors (type of housing), however, the differences between these regions were reduced. No geographical difference in the prevalence of eczema was observed. Thus, geographical differences in the prevalence of asthma and rhinitis in Singapore could in part be explained by demographic and socio-economic differences in the population.

Month of birth and childhood atopic diseases in the tropics.

The relationship between the month of birth and prevalence of diagnosed asthma, asthma-like symptoms (wheezing, nocturnal cough, and exercise wheezing), rhinitis, and eczema was investigated in four cohorts each of primary schoolchildren and secondary school (high school) adolescents in Singapore by questionnaire survey. Significantly increased prevalence rates of diagnosed asthma and asthma-like symptoms were observed in certain birth months of the year for two adolescent cohorts, while significant association between birth month and presence of symptoms of rhinitis was found in a cohort of 6-7-year-olds. However, when demographic factors were taken into consideration by multivariate analysis, only the association between asthma, asthma-like symptoms, and birth month remained significant in one of the adolescent cohorts. There was, therefore, only a weak association between the month of birth and atopic disease in our schoolchildren. The overall seasonal trends, however, did show two main seasons (March-May and September-November) associated with higher prevalence of these diseases.

Awareness of environmental issues and the acceptance of CFC-free inhalers.

With the recent availability of a chlorofluorocarbon (CFC)-free metered dose inhaler (MDI) (Airomir), a patient survey was carried out to evaluate awareness of the role of CFCs in our environment and acceptance of this new inhaler. A questionnaire survey was conducted on parents and guardians of 201 children. Depending on respondents' preference, the interview was conducted in English (71%), Chinese (23%), Malay (5%) or Tamil (1%). A 'taste' test was also conducted on 103 of these children. Only 13% (26/201) of parents/guardians were aware that MDIs contained CFCs. Although 70% of children were in favour of the new taste of the CFC-free inhaler, the cost of the new inhaler was an important consideration for parents and guardians in their decision to switch to the new inhaler. The majority (93%) were willing to switch if its cost were equivalent to their current inhaler. This study has provided pertinent information with regard to acceptance of CFC-free inhalers which should be considered when making the inevitable switch to environmentally friendly inhalers.