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PubMed2003

Endotoxin contamination contributes to the pulmonary inflammatory and functional response to Aspergillus fumigatus extract inhalation in heaves horses.

BACKGROUND: Mould extract inhalation challenges have been used extensively in the investigation of heaves. Such challenges have induced pulmonary neutrophilic inflammation and dysfunction, consistent with, but less severe than the natural disease. However, the method of mould extract production is likely to result in endotoxin contamination. OBJECTIVE: To investigate whether insufficient dose delivery was responsible for the shortfall in response to inhaled extract compared with natural disease, and whether endotoxin contamination of mould extract contributed to the pulmonary inflammation and dysfunction. METHODS: We measured the response of six heaves horses following inhalation of saline (placebo) and three doses of Aspergillus fumigatus extract. We then compared the response of six heaves horses to A. fumigatus extract inhalation before and after lipopolysaccharide (LPS) depletion. RESULTS: Inhalation challenge with 0.5, 1.6 and 5 mg of A. fumigatus extract resulted in a significant increase in bronchoalveolar lavage fluid (BALF) neutrophil ratio when compared with saline inhalation. Only 1.6 and 5 mg extract inhalation resulted in significant lung dysfunction compared with saline. There was no significant difference between 1.6 and 5 mg extract inhalation with respect to airway neutrophil numbers or lung function, suggesting a plateau in both measured responses. LPS depletion of 1.6 mg A. fumigatus extract resulted in a significant reduction in airway neutrophil numbers and increase in arterial oxygen tension. There was no significant difference between saline and the LPS-depleted A. fumigatus extract challenges with respect to neutrophil count and lung function. The reduction in airway neutrophil numbers was greater than would be predicted by extrapolation from previously reported soluble LPS dose-response inhalation experiments. CONCLUSION: This study supports a role for other inhalants, in addition to soluble components of A. fumigatus, in the aetiopathogenesis of heaves. Also the amplification in response to LPS when inhaled with A. fumigatus extract, suggests that the role of inhaled endotoxin in the pulmonary inflammation and dysfunction in naturally occurring heaves may currently be underestimated.

Animal Feed↗

PubMed2001

Determinants of an incorrect inhalation technique in patients with asthma or COPD.

OBJECTIVE: To determine the prevalence of an incorrect inhalation technique and to examine its determinants among primary care patients with asthma or chronic obstructive pulmonary disease (COPD). DESIGN: Cross-sectional study. SETTING: 28 general practitioners in The Netherlands. SUBJECTS: 558 asthma and COPD patients, aged 16-75 years. MAIN OUTCOME MEASURES: Inhalation technique was assessed using a standardised inhaler-specific checklist. Pulmonary function assessment and questionnaires were used to collect data about inhaler, patient and disease characteristics. RESULTS: Overall, 24.2% of the patients made at least one essential mistake in their inhalation technique. The type of inhaler appeared to be the strongest independent determinant of an incorrect inhalation technique. Compared to patients using the Diskhaler, patients using the Rotahaler/Spinhaler, Turbuhaler, Metered Dose Inhaler (MDI) or Cyclohaler/Inhaler-Ingelheim were at significantly higher risk of making inhalation mistakes (odds ratios (OR) were 16.08, 13.17, 11.60 and 3.27, respectively). Other significant determinants of an incorrect inhalation technique were low emotional quality of life (OR = 1.73) and being treated in a group practice (OR = 2.26). CONCLUSIONS: An incorrect inhalation technique is common among pulmonary disease patients in primary care. Our study suggests that especially patients using the Rotahaler/Spinhaler, Turbuhaler or MDI, patients with emotional problems and patients in a group practice are at increased risk for an incorrect inhalation technique.

Adolescent↗

PubMedDate not supplied

Bacterial colonization of nasal steroid inhalers in chronic rhinosinusitis.

BACKGROUND: The aim of this study was to determine if nasal steroid inhalers harbor bacteria. METHODS: Nasal steroid inhalers were randomly selected from an adult patient population with chronic rhinosinusitis. Swab cultures of the tip of the nasal inhaler were obtained and submitted for microbiological analysis. Contemporaneous control cultures were obtained from freshly opened nasal steroid inhalers. Comparisons were conducted between bacterial recovery rates and types of organisms recovered from the patient and control groups. RESULTS: Among 31 nasal inhalers in use, 14 inhalers (45%) were found to harbor bacteria. The most common organisms were coagulase negative Staphylococci (11 inhalers) followed by oral flora (2 inhalers) and bacillus species (1 inhaler). None of the 10 control cultures were found to harbor bacteria. Nasal steroid inhalers in use were more likely to have bacterial colonization than new inhalers (p = 0.008, chi-square). CONCLUSIONS: Nasal steroid inhalers may harbor pathogenic bacteria. Therefore, they may serve as a vehicle for subsequent reinfection.

Adult↗

PubMed1989

Comparison of intermittent and continuous inhalation provocation tests.

To improve standardization of inhalation provocation tests, two tests utilizing intermittent and continuous inhalation of methacholine aerosol were compared in five normal and ten asthmatic patients. During the intermittent inhalation test, methacholine aerosols with stepwise incremental concentrations were inhaled during tidal breathing for two minutes with a following 5-minute pause interval. Specific airway conductance (SGaw) and respiratory resistance (Rrs) were measured one-half, one and one-half, and five minutes after the end of each inhalation period. Specific airway conductance and Rrs were measured with the panting and forced oscillation methods, respectively. During the continuous inhalation test, the same stepwise incremental concentrations of methacholine aerosol were inhaled during tidal breathing for two minutes without a pause while Rrs was continuously measured. The cumulative dose of methacholine required to reduce SGaw by 35% of the baseline value (PD35 SGaw) during the intermittent inhalation test was significantly correlated with the cumulative methacholine dose required to reduce Grs (= 1/Rrs) by 35% of the baseline value during the continuous inhalation test (PD35 Grs) (r = .98). There was also a significant correlation between the slopes of the intermittent inhalation test and continuous inhalation test curves (r = .80). The results indicate that methacholine provocation can be measured as reliably using a simple continuous inhalation method as by a more complex intermittent one.

Adult↗

PubMedDate not supplied

The nicotine inhaler in smoking cessation.

BACKGROUND: Nicotine replacement therapy has been shown to improve success rates in smoking cessation treatment. However, the available products cause adverse effects, which prevent some smokers from using them. A new method of delivering nicotine via inhaler supplies nicotine orally through inhalation from a plastic tube. This mode of delivering nicotine resembles smoking, as it includes handling and active inhalation. OBJECTIVES: To assess the efficacy and safety of the nicotine inhaler as an aid in smoking cessation. METHODS: A 1-year, randomized, double-blind, placebo-controlled study was conducted in a smoking cessation clinic. Two hundred forty-seven smokers who smoked at least 10 cigarettes per day and who had previously made a serious attempt to stop smoking using nicotine chewing gum were recruited through advertisements. Randomization to treatment or control conditions were made at the first group session, with 123 participants receiving nicotine inhalers and 124 receiving placebo inhalers. The inhalers were distributed at the second session and participants were allowed to use the inhalers for 6 months. MAIN OUTCOME MEASURE: Biochemically verified continuous abstinence from smoking after 2 and 6 weeks and at 3, 6, and 12 months. RESULTS: Significantly more participants who had used the nicotine inhalers were continuously abstinent compared with those who had used the placebo inhalers. The respective success rates after 12 months were 28% and 18% (P = .046). At 6 months, 20 participants (16%) in the nicotine group were still using the inhaler, compared with 4 (3%) in the control group (P < .001). CONCLUSION: The nicotine inhaler was an effective smoking cessation aid that produced a few mild and transient adverse effects.

Adult↗

PubMed2006

Prescription bias and factors associated with improper use of inhalers.

Many different inhalers are available for delivering aerosol therapy in respiratory medicine. As a consequence, the prescribing physicians may have some difficulty tailoring the most suitable inhaler to each patient. This multicenter, observational study using a self-administered questionnaire analyzed the characteristics of a large sample of patients (n = 1,305; 55% females; mean age 57.4, with a range of 15-88 years; most suffering from asthma or chronic obstructive pulmonary disease [COPD]) familiar with several different types of inhalers in relation to their most commonly used delivery device. Data on the inhalation technique for 2,057 observations of 1,126 patients using device-specific checklists and factors associated to misuse were also evaluated. Prevalent usage of newer dry powder inhalers (DPIs) was significantly associated with male sex, higher education, better respiratory function, and prescription from a respiratory physician. Patients using DPIs had received less instruction by health caregivers and were more likely to have read the instruction leaflet than users of metered dose inhalers (MDIs). Under these conditions, inhaler misuse was common and similar for both pressurized metered dose inhalers (pMDIs) and DPIs. For both types of inhalers, misuse was significantly and equally associated to increased age, less education, and less instruction by health care personnel. We conclude that many doctors are not familiar with the relevant characteristics of currently available inhalers. The prescription of newer DPIs may be subjected to gender, socio-economic, and instruction bias. The simple change of device from the pMDI to the newer DPIs is not associated with improved inhalation technique.

Administration, Inhalation↗

PubMed2000

Combined lidocaine and salbutamol inhalation for airway anesthesia markedly protects against reflex bronchoconstriction.

BACKGROUND: Lidocaine inhalation, in subjects with bronchial hyperreactivity, attenuates evoked bronchoconstriction but also irritates airways. Whether salbutamol pretreatment can mitigate airway irritation and whether combined treatment offers more protection than treatment with either drug alone is unknown. Therefore, we evaluated the effects of the inhalation of lidocaine, salbutamol, lidocaine and salbutamol combined, and placebo on an inhalational histamine challenge. METHODS: Fifteen patients with mild asthma were selected by a screening procedure (ie, a provocative concentration of a substance [histamine aerosol of < 18 mg/mL] causing a 20% fall in FEV(1) [PC(20)]). On 4 different days after pretreatment with the inhalation of lidocaine (5 mg/kg), inhalation of salbutamol (1.5 mg), combined treatment, or placebo, the histamine challenge was repeated. RESULTS: The baseline FEV(1) after lidocaine inhalation but prior to the histamine challenge decreased by > 5% in 7 of 15 volunteers, with a mean (+/- SD) decrease from 3.82 +/- 0.90 to 3.54 +/- 0.86 L (p = 0.0054). The baseline PC(20) for histamine was 6.4 +/- 4.3 mg/mL. Both lidocaine and salbutamol inhalation significantly increased PC(20) more than twofold (14.9 +/- 13.7 and 16.8 +/- 10.9 mg/mL, respectively; p = 0, 0007) at a lidocaine plasma concentration of 0.7 +/- 0.3 microg/mL. Combined treatment quadrupled the PC(20) to 29.7 +/- 20.3 mg/mL (vs lidocaine, p = 0.002; vs salbutamol, p = 0.003). CONCLUSIONS: Thus, histamine-evoked bronchoconstriction, as a model of reflex bronchoconstriction, can be significantly attenuated by salbutamol or lidocaine inhalation. However, lidocaine inhalation causes significant initial bronchoconstriction. The combined inhalation of salbutamol and lidocaine prevents the initial bronchoconstriction observed with lidocaine alone and offers even more protection to a histamine challenge than either lidocaine or salbutamol alone. Therefore, the combined inhalation of lidocaine and salbutamol can be recommended to mitigate bronchoconstriction when airway instrumentation is required.

Administration, Inhalation↗

PubMed2005

Problems with inhaler use: a call for improved clinician and patient education.

Patient education is a critical factor in the use and misuse of medication inhalers. Inhalers represent advanced technology that is considered so easy to use that many patients and clinicians do not receive adequate training in their use. Between 28% and 68% of patients do not use metered-dose inhalers or powder inhalers well enough to benefit from the prescribed medication, and 39-67% of nurses, doctors, and respiratory therapists are unable to adequately describe or perform critical steps for using inhalers. Of an estimated 25 billion dollars spent for inhalers annually, 5-7 billion dollars is wasted because of inhaler misuse. Reimbursement and teaching strategies to improve patient education could substantially reduce these wasted resources. Problems with inhaler use, the cost of inhalers, and myths associated with inhalers are reviewed, with recommendations for strategies and techniques to better educate patients in inhaler use.

Administration, Inhalation↗

PubMed1999

Inhaled nitric oxide, oxygen, and alkalosis: dose-response interactions in a lamb model of pulmonary hypertension.

Inhaled nitric oxide (NO) is currently used as an adjuvant therapy for a variety of pulmonary hypertensive disorders. In both animal and human studies, inhaled NO induces selective, dose-dependent pulmonary vasodilation. However, its potential interactions with other simultaneously used pulmonary vasodilator therapies have not been studied. Therefore, the objective of this study was to determine the potential dose-response interactions of inhaled NO, oxygen, and alkalosis therapies. Fourteen newborn lambs (age 1-6 days) were instrumented to measure vascular pressures and left pulmonary artery blood flow. After recovery, the lambs were sedated and mechanically ventilated. During steady-state pulmonary hypertension induced by U46619 (a thromboxane A2 mimic), the lambs were exposed to the following conditions: Protocol A, inhaled NO (0, 5, 40, and 80 ppm) and inspired oxygen concentrations (FiO2) of 0.21, 0.50, and 1.00; and Protocol B, inhaled NO (0, 5, 40, and 80 ppm) and arterial pH levels of 7.30, 7.40, 7.50, and 7.60. Each condition (in randomly chosen order) was maintained for 10 min, and all variables were allowed to return to baseline between conditions. Inhaled NO, oxygen, and alkalosis produced dose-dependent decreases in mean pulmonary arterial pressures (P < 0.05). Systemic arterial pressure remained unchanged. At 5 ppm of inhaled NO, alkalosis and oxygen induced further dose-dependent decreases in mean pulmonary arterial pressures (P < 0.05). At inhaled NO doses > 5 ppm, alkalosis induced further dose-independent decreases in mean pulmonary arterial pressure, while oxygen did not. We conclude that in this animal model, oxygen, alkalosis, and inhaled NO induced selective, dose-dependent pulmonary vasodilation. However, when combined, a systemic arterial pH > 7.40 augmented inhaled NO-induced pulmonary vasodilation, while an FiO2 > 0.5 did not. Therefore, weaning high FiO2 during inhaled NO therapy should be considered, since it may not diminish the pulmonary vasodilating effects. Further studies are warranted to guide the clinical weaning strategies of these pulmonary vasodilator therapies.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2003

Methemoglobin formation in children with congenital heart disease treated with inhaled nitric oxide after cardiac surgery.

OBJECTIVE: Inhaled nitric oxide (NO) is used as a therapy of pulmonary hypertension in children after cardiac surgery. Hemoglobin binds to NO with great affinity and forms methemoglobin by oxidation in the erythrocyte. Once produced, methemoglobin is unable to transport and unload oxygen in the tissues. The amount of available hemoglobin in the body for oxygen transport is thereby reduced. Anemia, acidosis, respiratory compromise and cardiac disease may render patients more susceptible than expected for a given methemoglobin level. The goal of the present study was to review the cumulative effect of inhaled NO on methemoglobin formation in critically ill children. We therefore looked for methemoglobin levels in children with congenital heart disease after cardiac surgery who were treated with inhaled NO in a range of 5-40 ppm. METHODS: We retrospectively reviewed the medical charts of 38 children with congenital heart disease after cardiac surgery. We extracted demographic data and physiological measurements at the following time points: (1) T0 = before starting inhaled NO therapy, (2) T1 = 24 h after the beginning of inhaled NO therapy, (3) T2 = half-time therapy, (4) T3 = end of therapy, (5) T4 = 24 h after finishing inhaled NO therapy. RESULTS: The median duration of inhaled NO therapy was 5.5 days (interquartile range 6, range 2-29), NO concentrations at T1 and T2 were 16 ppm (10, 5-40) and 12.5 ppm (12.3, 2-40), respectively. The median cumulative dose of inhaled NO was 1699 ppm (2313, 193-7018). Methemoglobin levels increased moderately, but significantly, during therapy ( T0 vs T1 p<0.05 and T0 vs T2 p<0.001). The highest methemoglobin level measured was 3.9%. Methemoglobin levels correlated positively with the inhaled NO doses applied at T1 ( r(2)=0.8376; p<0.01) and at T2 ( r(2)=0.8945; p<0.01). At T1 the methemoglobin level correlated negatively with the T1 blood pH value. The overall mortality rate was 13.2% (5 of 38 study patients died). There was no significant difference in methemoglobin levels between survivors and non-survivors. CONCLUSION: We conclude from our data that the use of inhaled NO therapy for children with congenital heart disease after cardiac surgery in the described range of 5-40 ppm, resulting in a maximum of 4% methemoglobin blood level, is feasible and safe. However, we recommend the use of the minimal effective dose of inhaled NO and continuous monitoring of methemoglobin levels, especially in cases of anemia or sepsis in critically ill children.

Administration, Inhalation↗

PubMedDate not supplied

Lidocaine inhalation attenuates the circulatory response to laryngoscopy and endotracheal intubation.

STUDY OBJECTIVE: To evaluate the effect of lidocaine inhalation on the circulatory response to direct laryngoscopy and endotracheal intubation. DESIGN: Prospective, randomized study. SETTING: Operating theater at a public hospital. PATIENTS: Eighty patients (ASA physical status I and II ages 25 to 45 years) scheduled for major abdominal surgery. INTERVENTIONS: In the first stage, 40 patients were randomly assigned to receive inhalation of either lidocaine 40 mg or a 0.9% solution of sodium chloride (placebo). In the second stage, the next 20 consecutive patients received inhalation of lidocaine 120 mg, and another 20 consecutive patients received intravenous (IV) lidocaine 1 mg/kg. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure rose significantly in the i.v. lidocaine group (21.2 mmHg; p < 0.05), the saline inhalation group (29.2 mmHg; p < 0.05), and the lidocaine 40 mg inhalation group (22.9 mmHg; p < 0.05), but not in the lidocaine 120 mg inhalation group (10.1 mmHg). The heart rate (HR) response to intubation with lidocaine inhalation was dose dependent. In the saline inhalation group, HR increased by 15.6 beats per minute (bpm) (p < 0.05); in the lidocaine 40 mg inhalation group, HR increased by 9.1 bpm (p < 0.05); and in the lidocaine 120 mg inhalation group, HR increased by only 3.1 bpm. CONCLUSION: Inhalation of lidocaine 120 mg prior to induction of anesthesia is an effective, safe, and convenient method to attenuate the circulatory response to laryngoscopy and endotracheal intubation.

Adult↗

PubMed2006

Impact of two sequential drug cost-sharing policies on the use of inhaled medications in older patients with chronic obstructive pulmonary disease or asthma.

BACKGROUND: Evaluations of drug cost-sharing policies within the same population are needed for a fair comparison of different options. OBJECTIVE: The aim of this work was to analyze the impact of 2 changes in a public drug insurance plan on the use of inhaled medications in British Columbia (BC), Canada. METHODS: Data for the period from 1997 to 2004 were used to assess whether changes in the use of steroid, beta2-agonist, and anticholinergic inhalers were associated with insurance-plan changes in a large, natural experiment involving all BC residents aged>or=65 years. The 3 sequential policies included full coverage, fixed copayments at the beginning of 2002, and 25% coinsurance with an income-based deductible beginning May 1, 2003. Linkable prescription, physician billing, hospitalization, and mortality records were obtained from the BC Ministry of Health Services. From the total population of residents aged>or=65 years, we extracted data for all patients to whom inhaled steroids, beta2-agonists, or anticholinergics were dispensed on or after January 1, 1997. Multivariable linear regression was used to estimate inhaler use during a 60-month baseline period and during implementation of the subsequent copayment and coinsurance plus deductible policies. We used logistic regression to identify predictors of initiation and cessation use of inhaled medications among older patients. RESULTS: Use declined for inhaled steroids (-12.3%; P<0.001), inhaled anticholinergics (-12.2%; P<0.001), and inhaled beta2-agonists (-5.8%; P<0.001). Patients with new diagnoses of asthma or chronic obstructive pulmonary disease were 25% (95% CI, 14%-31%) less likely to initiate treatment with inhaled steroids when covered by the copayment or coinsurance plus deductible policies than when they had full coverage. Chronic users of inhaled steroids were 47% (95% CI, 40%-55%) more likely to cease treatment when they were covered by the copayment policy and 22% (95% CI, 15%-29%) more likely to cease when covered by the coinsurance plus deductible policy than when they had full coverage. CONCLUSIONS: The copayment and coinsurance plus deductible policies were associated with significant reductions in use of inhaled medications, mostly due to decreased initiation and increased cessation rates. However, the consequences of these policies on health outcomes have not yet been determined.

Administration, Inhalation↗

PubMed1997

Dose response to inhaled nitric oxide in pediatric patients with pulmonary hypertension and acute respiratory distress syndrome.

OBJECTIVE: To determine the pulmonary vascular functional dose response to inhaled nitric oxide (NO) for infants and children with acute respiratory distress syndrome and pulmonary artery hypertension. DESIGN: Prospective, clinical observational study. SETTING: Thirteen-bed pediatric intensive care unit at a 168-bed children's hospital. PATIENTS: Infants and children requiring mechanical ventilation with an oxygenation index greater than 10. METHODS: Children with severe acute respiratory distress syndrome received inhalation therapy with NO after conventional mechanical ventilation failed to result in improvement. Inhaled NO was sequentially titrated from 10 parts per million to 20, 40, 60, and 80 ppm at 10-minute intervals. A reduction of at least 30% in the pulmonary vascular resistance index (PVRI), or a reduction in mean pulmonary artery pressure of at least 10%, or an increase in the hypoxemia score of at least 20%, or a decrease in the oxygenation index of at least 20% from pretreatment values was considered a therapeutic response. After sequential titration, children who responded received continuous inhaled NO at the lowest dose associated with a therapeutic response. RESULTS: Fourteen children received 15 trials with inhaled NO (median age, 63.4 months; range, 0.4 to 201 months). One patient's condition deteriorated during the titration phase, unrelated to NO treatment, and the patient was withdrawn from the study protocol. The mean (+/- SD) pretreatment oxygenation index was 35 +/- 15, which decreased to 32 +/- 20 at 80 ppm of inhaled NO (p = 0.01). Ten children had pulmonary artery catheter measurements. The PVRI decreased by 30% or greater in seven children (70%). One child had a minimal decrease in PVRI during the titration phase but demonstrated an increase of more than 30% after NO therapy was discontinued. Mean pretreatment PVRI (270 +/- 106) decreased to 207 +/- 92 dynes/sec per cubic centimeter per square meter at 80 ppm of inhaled NO (p = 0.06). Pretreatment mean pulmonary artery pressure (31 +/- 7) decreased to 28 +/- 5 mm Hg at 80 ppm of inhaled NO (p = 0.04). Six trials (43%) showed an increase of 20% or greater in their hypoxemia score. Maximum improvement in the hypoxemia score and reduction in OI, PVRI, and mean pulmonary artery pressure occurred at 20 to 40 ppm of NO. Ten trials led to continuous inhaled NO therapy ranging from 7 to 661.5 hours, with a median of 47 hours. Systemic hypotension was not observed in any patient, and the maximum methemoglobin level was 5%. CONCLUSION: Inhaled NO appears to be a safe, although variably effective, therapy for the treatment of infants and children with acute respiratory distress syndrome. The maximum dose response occurs between 20 and 40 ppm of inhaled NO. Systemic side effects did not occur in any child who received NO therapy.

Administration, Inhalation↗

PubMed2002

Treatment satisfaction in type 2 diabetes: a comparison between an inhaled insulin regimen and a subcutaneous insulin regimen.

BACKGROUND: In patients with type 2 diabetes, published data suggest that glycemic control can be achieved as effectively with an inhaled insulin regimen (preprandial inhaled intrapulmonary insulin plus a single bedtime Ultralente injection) as with a conventional subcutaneous insulin regimen involving 2 to 3 injections per day. It is unknown whether inhalation delivery of insulin improves patient satisfaction. OBJECTIVE: Our objective was to compare patient satisfaction between an inhaled insulin regimen and a subcutaneous insulin regimen. METHODS: This was a 12-week randomized, open-label, parallel-group, controlled trial in patients with type 2 diabetes. They were randomized to receive either a subcutaneous insulin regimen (split/mixed insulin with 2 to 3 injections daily) or an inhaled insulin regimen (inhaled insulin before meals and a single Ultralente insulin injection at bedtime). Change in glycosylated hemoglobin (HbA1c) from baseline to week 12 was the study's primary end point. At baseline and week 12, patients completed a questionnaire (Patient Satisfaction with Insulin Therapy Questionnaire) covering attributes of patient satisfaction. Treatment regimens were compared on each item with the Wilcoxon rank sum test and on the overall score with a t test. RESULTS: Fifty-one patients (age range, 35-65 years) participated in the study, 26 receiving inhaled insulin and 25 receiving subcutaneous insulin. Forty-seven patients (22 inhaled insulin, 25 subcutaneous insulin) completed the satisfaction questionnaire. The mean percent improvement in overall satisfaction with an inhaled insulin regimen (31%; 95% CI, 14-50) was significantly greater (P < 0.05) than that with a subcutaneous insulin regimen (13%; 95% CI, 7-19). Increases in overall satisfaction correlated with improvements in glycemic control (r = 0.30; P < 0.05). Both treatment regimens experienced a mean HbA1c reduction of approximately 0.7%. Although patient satisfaction was the chief focus of this article, these results should be considered exploratory, as the trial was powered prospectively for HbA1c values (the primary end point) and not for patient satisfaction. CONCLUSIONS: Administration of an inhaled insulin regimen may offer the first practical, noninvasive alternative to insulin injections. In the patients with type 2 diabetes studied, an inhaled insulin regimen with the need for only 1 subcutaneous injection at bedtime appeared to offer more ease of use, comfort, and convenience, as well as greater overall satisfaction, than a subcutaneous insulin regimen of 2 to 3 injections daily.

Administration, Inhalation↗

PubMed1996

Are young adults with asthma treated sufficiently with inhaled steroids? A population-based study of prescription data from 1991 and 1994.

1. We conducted a descriptive cross-sectional study of asthma therapy among young adults to assess to what extent the current guidelines for asthma therapy have been implemented. In particular, we examined the use of inhaled corticosteroids in heavy users of inhaled beta-adrenoceptor agonists. 2. Data were retrieved from a population-based prescription database. For each of the years 1991 and 1994, all 20 to 44-year-olds who redeemed anti-asthma medication in the Odense area (210,000 inhabitants) were studied. 3. We identified the number of users and total sales volume for specific anti-asthma medications in defined daily doses (DDD) as well as the number of users and median annual doses of common regimens. Combined use of inhaled corticosteroids and inhaled beta-adrenoceptor agonists was also described. 4. The annual sales volume of anti-asthma drugs increased by 23% to 927,636 DDD from 1991 to 1994. Inhaled corticosteroids were mainly responsible for this with a 52% increase in number of users and an 88% increase in DDD. Inhaled beta-adrenoceptor agonists used in monotherapy remained the most popular regimen in 1994 (1685 users = 39%). Inhaled corticosteroids in combination with inhaled beta-adrenoceptor agonist were the second most popular regimen in 1994 (1308 users = 30%), increasing by 64% as compared with 1991. However, among patients with an annual use of inhaled beta-adrenoceptor agonist of 200 DDD (1600 "puffs') or more the percent of patients not receiving inhaled corticosteroids at all only fell from 37 to 33%. Though the number of patients being treated with inhaled corticosteroids has increased, there is still evidence of a substantial underuse.

Administration, Inhalation↗

PubMed1999

Relative bioavailability of sodium cromoglycate to the lung following inhalation, using urinary excretion.

AIMS: To determine if a urinary excretion method, previously described for salbutamol, could also indicate the relative bioavailability of sodium cromoglycate to the lung following inhalation from a metered dose inhaler. Method Inhaled (INH), inhaled+oral charcoal (INHC), oral (ORAL) and oral+oral charcoal (ORALC) 20 mg doses of sodium cromoglycate were given via a randomised cross-over design to 11 healthy volunteers trained on how to use a metered dose inhaler. Urine samples were collected at 0.0, 0.5, 1.0 and up to 24 h post dosing and the sodium cromoglycate urinary concentration was measured using a high performance liquid chromatographic method. RESULTS: No sodium cromoglycate was detected in the urine up to 24 h following ORALC dosing. A mean (s.d.) of 3.6 (4.3) microg, 10.4 (10.9) microg and 83.7 (71.1) microg of the ORAL dose was excreted, in the urine, during the 0.5, 1.0 and 24 h post dose collection periods, respectively. Following INH dosing, the renal excretion was significantly higher (P<0.01) with 32.9 (14.5) microg, 61.2 (28.3) microg and 305.6 (82.3) microg excreted, respectively. The SCG excreted at 0.5, 1.0 and 24 h collection periods following INHC dosing were 26.3 (8.4) microg, 49.3 (18.1) microg and 184.9 (98.4) microg, respectively. There was no significant difference between the excretion rate of sodium cromoglycate following INHC when compared with INH dosing in the first 0.5 and 1.0 h. CONCLUSIONS: The urinary excretion of sodium cromoglycate in the first 0.5 h post inhalation can be used to compare the relative lung deposition of two inhaled products or of the same product using different inhalation techniques. This represents the relative bioavailability of sodium cromoglycate to the lung following inhalation. Similar 24 h urinary excretion of sodium cromoglycate can be use to compare the total dose delivered to the body from two different inhalation products/inhalation methods. This represents the relative bioavailability of sodium cromoglycate to the body following inhalation. Because of the lack of difference between the INH and INHC in the first 0.5 h, the use of activated charcoal is not necessary when this method is used to compare the relative lung bioavailability of different products or techniques.

Administration, Inhalation↗

PubMed1999

Inhaled insulin.

Inhalation is a potentially viable route of insulin administration. This treatment is being tested but has not been approved by the United States Food and Drug Administration (FDA). The lung airways contain bronchial tubes, which are impermeable to insulin and alveoli, from which insulin can be absorbed into the circulation. Inhaled asthma medications deposit before reaching the alveoli. Novel devices can deliver insulin particles via slow even breaths into the alveoli. An aerosol of either powdered or solubilized insulin can be released mechanically or electronically. Pulmonary toxicity due to inhaled insulin has not been reported, but no chronic use studies have been conducted. The efficiency of insulin delivery by inhalation may be compromised by: (1) losses within the device and the environment; (2) deposition onto the throat and bronchial tubes; and (3) incomplete absorption from the alveoli. With current delivery technology, the maximum possible delivery efficiency is approximately 30%. The peak activity of inhaled regular insulin occurs at 60 minutes, which is similar to that of subcutaneous lispro insulin. Inhaled long-acting insulin is in early development. Studies comparing sequentially administered subcutaneous and inhaled regular insulins have demonstrated significantly reproducible glucose-lowering effects of inhaled insulin. In type 1 and insulin-treated type 2 patients, substitution of premeal inhaled insulin for subcutaneous insulin has resulted in no significant change in control. In a series of patients with type 2 diabetes failing oral agents, addition of premeal inhaled insulin resulted in significantly improved control. Inhaled insulin will become established if ongoing studies continue to demonstrate this technology to be safe and effective.

Administration, Inhalation↗

PubMed2003

Acquisition and short-term retention of inhaler techniques require intact executive function in elderly subjects.

BACKGROUND: patients with dementia are almost invariably unable to use any form of inhaler. Some elderly patients are unable to learn to use a metered dose inhaler or Turbohaler despite a normal abbreviated mental test score. Studies have shown that in many people this is due to unrecognised cognitive impairment and/or dyspraxia. The executive domains of cognition are particularly important in planning and sequencing; it might be expected therefore that disordered frontal (executive) function could be a predictor of poor inhaler technique in subjects with no overt features of dementia. OBJECTIVE: to explore the relationship between cognitive, and executive, function and the ability to acquire metered dose inhaler and Turbohaler technique in old age. DESIGN: a prospective randomised observational study with blinded evaluation. SUBJECTS: 30 inhaler-naive inpatients (21 female) with a mean age of 85 (range 75-94) and having a normal (8-10) abbreviated mental test score. METHODS: subjects received standardised metered dose inhaler and Turbohaler training and were scored on an analogue scale (for metered dose inhaler) or for competence (Turbohaler) the following day. The Mini-Mental State Examination and EXIT25 (for executive function) were performed by separate observers. RESULTS: significant correlation was found between the metered dose inhaler score and Mini-Mental State Examination (r 0.540, P<0.002) and EXIT25 (r -0.702, P<0.0001). Threshold effects emerged for the metered dose inhaler in that 18/19 with a competent score compared to 2/11 scored as incompetent had a Mini-Mental State Examination of >23 (P<0.01) and 19/19 compared to 0/11 had an EXIT25 of <15 (P<0.01). Similarly, for the Turbohaler 21/21 of the competent subjects had a Mini-Mental State Examination of >23 compared with 3/9 incompetent subjects (P<0.01), with 21/21 competent compared with 0/9 incompetent having an EXIT25 <15 (P<0.01). CONCLUSION: acquisition and short-term retention of metered dose inhaler and Turbohaler techniques is unlikely to be successful in frail elderly people who have an abnormal Mini-Mental State Examination and/or EXIT25 test. The latter test, when abnormal, is probably the superior predictor of inability to learn inhaler techniques.

Aged↗