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Variability in Delivered Dose from Pressurized Metered-Dose Inhaler Formulations Due to a Delay Between Shake and Fire.

BACKGROUND: Pressurized metered-dose inhalers (pMDIs) should be shaken before use to prevent creaming or sedimentation of the drugs in solution; however, data published on this topic are limited, and it is rarely specified how soon after shaking the device should be actuated. Delays between shaking and firing the pMDI have previously been shown to cause significant inhomogeneity in delivered dose. We studied the effect of various shake-fire delays on the drug delivered from five commercially available pMDIs commonly prescribed for asthma and chronic obstructive pulmonary disease to assess the potential variability in delivered dose.

METHODS: The pMDI formulations tested were the Flovent HFA, Ventolin Evohaler, Airomir Inhaler, and Symbicort (suspension pMDIs), and the QVAR 100 Inhaler (solution pMDI). Each pMDI was shaken for 5 seconds before attachment to a dosage unit sampling apparatus collection tube and filter, and it was actuated once with shake-fire delays of 0, 5, 10, 20, 30, 40, 50, and 60 seconds. Analysis of the eluates from the collection tubes and filters was performed by using high-performance liquid chromatography. Three of each pMDI were tested twice with each time delay.

RESULTS: All of the suspension pMDIs produced variable amounts of drug over the shake-fire delays tested. A comparison of the delivered doses after the 0- and 60-second delays showed that the drug delivered increased for the Flovent HFA (320%), Ventolin Evohaler (346%), and Airomir Inhaler (230%) pMDIs; decreased for the Symbicort budesonide (75%) and formoterol fumarate (76%) pMDI; and remained consistent for the QVAR 100 Inhaler pMDI.

CONCLUSIONS: The amount of drug delivered can vary widely over different shake-fire delays with suspension pMDIs. Therefore, guidance should be given to users/caregivers on the timing of firing after shaking their device, particularly with pediatrics, who may take time to become receptive to accepting their medication after pMDI shaking and before dose administration.

Medications for Chronic Asthma.

Chronic asthma is a major health concern for children and adults worldwide. The goal of treatment is to prevent symptoms by reducing airway inflammation and hyperreactivity. Step-up therapy for symptom control involves initiation with low-dose treatment and increasing intensity at subsequent visits if control is not achieved. Step-down therapy starts with a high-dose regimen, reducing intensity as control is achieved. Multiple randomized controlled trials have shown that inhaled corticosteroids are the most effective monotherapy.

Other agents may be added to inhaled corticosteroids if optimal symptom control is not initially attained. Long-acting beta2 agonists are the most effective addition, but they are not recommended as monotherapy because of questions regarding their safety. Leukotriene receptor antagonists can be used in addition to inhaled corticosteroids, but they are not as effective as adding a long-acting beta2 agonist. Patients with mild persistent asthma who prefer not to use inhaled corticosteroids may use leukotriene receptor antagonists as monotherapy, but they are less effective. Because of their high cost and a risk of anaphylaxis, monoclonal antibodies should be reserved for patients with severe symptoms not controlled by other agents. Immunotherapy should be considered in persons with asthma triggered by confirmed allergies if they are experiencing adverse effects with medication or have other comorbid allergic conditions.

Many patients with asthma use complementary and alternative agents, most of which lack data regarding their safety or effectiveness.

Obesity: systemic and pulmonary complications, biochemical abnormalities, and impairment of lung function

Abstract Obesity is currently one of the major epidemics of this millennium and affects individuals throughout the world. It causes multiple systemic complications, some of which result in severe impairment of organs and tissues. These complications involve mechanical changes caused by the accumulation of adipose tissue and the numerous cytokines produced by adipocytes. Obesity also significantly interferes with respiratory function by decreasing lung volume, particularly the expiratory reserve volume and functional residual capacity. Because of the ineffectiveness of the respiratory muscles, strength and resistance may be reduced. All these factors lead to inspiratory overload, which increases respiratory effort, oxygen consumption, and respiratory energy expenditure. It is note...

Dry-powder inhalers in patients with persistent airflow limitation: usability and preference

ConclusionsThe possibility of grading objectively the performance of different DPIs in terms of their usability and therapeutic convenience in daily life represents a crucial operational opportunity to pursue. To note that a substantial discrepancy  exists between the patients’ belief “at glance” and the patients’ effective usability with can be registered with some devices. From a general point of view, devices requiring less manual actions for their actuation confirmed their better usability and proper handling after less attempts. In particular, Genuair came out as the most preferred DPI also when several different aspects of preference and usability are assessed objectively and compared. (Source: Multidisciplinary Respiratory Medicine)

Acute pulmonary embolism: mortality prediction by the 2014 European Society of Cardiology risk stratification model

The European Society of Cardiology (ESC) has proposed an updated risk stratification model for death in patients with acute pulmonary embolism based on clinical scores (Pulmonary Embolism Severity Index (PESI) or simplified PESI (sPESI)), right ventricle dysfunction (RVD) and elevated serum troponin (2014 ESC model).

We assessed the ability of the 2014 ESC model to predict 30-day death after acute pulmonary embolism. Consecutive patients with symptomatic, confirmed pulmonary embolism included in prospective cohorts were merged in a collaborative database. Patients’ risk was classified as high (shock or hypotension), intermediate-high (RVD and elevated troponin), intermediate-low (RVD or increased troponin or none) and low (sPESI 0). Study outcomes were death and pulmonary embolism-related death at 30 days.

Among 906 patients (mean±sd age 68±16, 489 females), death and pulmonary embolism-related death occurred in 7.2% and 4.1%, respectively. Death rate was 22% in "high-risk" (95% CI 14.0–29.8), 7.7% in "intermediate-high-risk" (95% CI 4.5–10.9) and 6.0% in "intermediate-low-risk" patients (95% CI 3.4–8.6). One of the 196 "low-risk" patients died (0.5%, 95% CI 0–1.0; negative predictive value 99.5%).

By using the 2014 ESC model, RVD or troponin tests would be avoided in about 20% of patients (sPESI 0), preserving a high negative predictive value. Risk stratification in patients at intermediate risk requires further improvement.

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