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Progression Of Asthma That Is Nonresponsive To Treatment

Effects Of Asthma On The Cardiovascular System

Asthma & COPD Treatment / Pharmacology (Inhaler Progression)

Acute, severe asthma alters profoundly the cardiovascular status and function . In expiration, because of the effects of dynamic hyperinflation, the systemic venous return decreases significantly, and again rapidly increases in the next respiratory phase. Rapid right ventricular filling in inspiration, by shifting the interventricular septum toward the left ventricle, may lead to left ventricular diastolic dysfunction and incomplete filling. The large negative intrathoracic pressure generated during inspiration increases left ventricular after-load by impairing systolic emptying. Pulmonary artery pressure may also be increased due to lung hyperinflation, thereby resulting in increased right ventricular afterload. These events in acute, severe asthma may accentuate the normal inspiratory reduction in left ventricular stroke volume and systolic pressure, leading to the appearance of pulsus paradoxus . A variation greater than 12 mmHg in systolic blood pressure between inspiration and expiration represents a sign of severity in asthmatic crisis. In advanced stages, when ventilatory muscle fatigue ensues, pulsus paradoxus will decrease or disappear as force generation declines. Such status harbingers impeding respiratory arrest.

Postdischarge Therapy And Importance Of An Action Plan

Before discharge from the hospital or the emergency department, arrangements for follow-up within 12 weeks should be made for patients. Patients who are hospitalized for their asthma may be especially receptive to information and advice about how to control symptoms and avoid future exacerbations. Health-care providers or an asthma educator should provide detailed education to all patients before discharge. Discussion should assure that the patient understands the cause of his or her exacerbation, modifiable risks factors , the purpose and correct use of medications, and an updated asthma action plan. The action plan should identify each discharge medication, the dose, and frequency. It should also outline how often to take the quick reliever medications if symptoms increase or PEF/FEV1 decreases, when to consider taking oral corticosteroids, and how to reach their primary care provider or obtain emergency care if their asthma does not respond to a step-up in therapy. Patients > 5 y of age usually are discharged with a flow meter, with instructions to keep track of their values until they are seen in follow-up. This is especially important for patients with brittle asthma or for patients identified at risk for near-fatal exacerbations of asthma. Patients should demonstrate the proper use of their inhalers and be discharged with a sufficient quantity of medication to last for at least 12 months.

Management Of Status Asthmaticus In The Icu

Patients admitted to the ICU include individuals who require ventilator support or those with severe asthma for whom therapy failed. Most often they have refractory hypercapnia, persisting or worsening hypoxemia, deteriorating PEF/FEV1, drowsiness, confusion, or impending signs of respiratory arrest. Elective intubation by an experienced clinician is always recommended as soon as signs of deterioration are present. Intubation and mechanical ventilation may lead to hypotension and barotrauma secondary to high positive intrathoracic pressures. Care must be taken to assure that intravascular volume is adequate before intubation, and a bolus of intravenous normal saline solution is often recommended before initiation of mechanical ventilation.

Although there are no studies that determined the optimal mode of mechanical ventilation, it seems prudent to use the mode with which one is most familiar. Most researchers have recommended an initial minute ventilation of 90130 mL/kg ideal body weight , with further adjustments based on pH and the plateau airway pressure. Based on studies by Tuxen and Lane and Peters et al, we usually use a tidal volume of 89 mL/kg with a breathing frequency of 1014 breaths/min, a flow of 100 L/s, and 0 PEEP. However, many institutions prefer to use tidal volumes of 68 mL/kg ideal body weight., We adjust the setting to maintain a plateau pressure of 30 cm H2O and judiciously adjust ventilator-applied PEEP based on its ability to lower intrinsic PEEP.

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Box 1 Criteria For Administration Of Omalizumab4445

  • Positive result on skin testing or in vivo reactivity to at least one perennial aeroallergen
  • Baseline immunoglobulin E levels of 30700 IU/mL
  • Weight 20150 kg
  • Calculated dose of omalizumab < 750 mg
  • Severe or inadequately controlled asthma, as defined by frequent exacerbations or the need for daily or frequent oral corticosteroids, despite appropriate environmental control, smoking cessation, patient education and consistent therapy with inhaled corticosteroid at a minimum daily dose of 500 g of fluticasone or equivalent plus adjunctive therapy

Before therapy with omalizumab is initiated, the patient should be assessed by a specialist. The response to omalizumab should be evaluated at 6 months and therapy discontinued for those who have not benefited. There is currently insufficient evidence to recommend omalizumab therapy for children with asthma .

Molecular Mechanisms Of Steroid

Anti-inflammatory effects of glucocorticoids are mediated by binding to the GR isoform GR, followed by the translocation of GR from the cytoplasm to the nucleus to regulate gene transcription . Whereas the GR isoform located in the nucleus does not bind to steroids, and also attenuates GR function . A primary mechanism of steroid-resistance in SA is by the dysregulation of GR function, which can be mediated by the cytokines involved in the pathobiology of SA . For example, a primary mode of action of TNF in SA is to promote increased expression of the GR isoform, which changes the GR/GR ratio making GR the dominant isoform thus resulting in steroid-resistance . Similarly, Th17-derived IL-17 induces the expression GR to mediate steroid resistance . IFN together with IL-27 suppresses the nuclear translocation of GR in response to glucocorticoids, to induce the steroid-refractory phenotype and AHR in SA . These studies clearly demonstrate that specific cytokines that are integrally associated with the various immunophenotypes of SA can facilitate dysregulation of GR-mediated response to steroids .

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What Are The Stages Of Asthma

Asthma can be either intermittent or persistent. When symptoms arise occasionally, a person has intermittent asthma. Symptoms of persistent asthma occur more often.

The four main asthma stages are:

  • severe persistent

These classifications are for people with asthma who do not take long-term controller medication.

The symptoms of asthma are the same at every stage, but their frequency and severity differ.

The main symptoms of asthma include:

We explore each asthma stage in detail below.

Natural History Of Asthma

Describing the natural history of asthma poses the same challenges as defining asthma. This is due to the heterogeneity of the airway diseases unified under the asthma label . Thus, the natural history may follow different paths of disease progression, including lung function decline, remission, reoccurrence, morbidity and mortality.

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Moderate To Severe Persistent Asthma: Step 4

As symptoms of moderate persistent asthma become more severe, the preferred controller medications change.

Options for controller medications for moderate to severe persistent asthma include:

  • a medium-dose ICS plus a LABA, which is the preferred method
  • a medium-dose ICS plus an LTRA
  • a medium-dose ICS plus theophylline, which is a less common, less effective choice

People can also use a SABA inhaler when needed to relieve symptoms.

Second Stage: Mild Persistent Asthma

Asthma longterm treatment | Respiratory system diseases | NCLEX-RN | Khan Academy

Although this stage is still relatively mild, asthma is beginning to become more noticeable and starting to interfere with your quality of life.

Symptoms. In mild persistent asthma, daytime symptoms are occurring 3 to 6 times a week. Nighttime symptoms interfere with sleep nearly every week, or 3 to 4 times a month. Flare-ups are more severe and may affect activity levels.

Lung function tests. As with intermittent asthma, the FEV1 is 80% or more above normal values. Peak flow readings show less than 20-30% variability.

Treatment. A low dose inhaled steroid will be used as a controller medication to prevent and control symptoms. Less common alternatives might include cromolyn, a leukotriene receptor antagonist , or theophylline. The doctor will also prescribe a quick-relief inhaler for flare-ups.

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Box 2 Key Messages For Treatment Of Asthma Unresponsive To Usual Care

This article is the fourth in a 7-part case study series that was developed as a knowledge translation initiative of the Canadian Thoracic Society Asthma Committee. The series aims to educate and inform primary care providers and nonrespiratory specialists about the diagnosis and management of asthma. The key messages presented in the cases are not clinical practice guidelines but are based on a review of the most recent scientific evidence available. Financial support for the publication of this series has been provided, in part, by the Canadian Thoracic Society.

Subcutaneous Epinephrine And Terbutaline

Subcutaneous administration of epinephrine or terbutaline should be considered, in patients not responding adequately to continuous nebulised salbutamol, and in those patients unable to cooperate It should also be attempted in intubated patients not responding to inhaled therapy. Epinephrine may also be delivered effectively down the endotracheal tube in extreme situations . Subcutaneously, 0.30.4 ml of epinephrine can be administered every 20 min for three doses . Terbutaline can be administered subcutaneously or as intravenous infusion starting at 0.050.10 g/kg per min . When administered subcutaneously, however, terbutaline loses its -selectivity and offers no advantages over epinephrine . Terbutaline administered subcutaneously should be preferred only in pregnancy because it appears safer . Subcutaneous administration of epinephrine or terbutaline should not be avoided or delayed since it is well tolerated even in patients older than 4050 years with no history of cardiovascular disease . Intravenous administration of -agonists is also an option in extreme situations and should be considered in the treatment of patients who have not responded to inhaled or subcutaneous treatment, and in whom respiratory arrest is imminent, or in patients not adequately ventilated and severely hyperinflated, despite optimal setting of the ventilator.

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Is There Anything I Can Do To Prevent An Attack

Theres no way to completely prevent severe asthma attacks if you have asthma. However, there are several things you can do to greatly reduce your risk of having one.

The most important step is sticking with the treatment plan recommended by your doctor. Even if your symptoms seem to be improving and you arent having any attacks, dont stop any treatments until your doctor tells you to do so.

Other preventive measures you can take include:

  • Using a peak flow monitor. This is a portable device that measures how much air comes out of your lungs when you quickly exhale. Keep track of your readings to see if you notice any patterns. Buy a peak flow monitor here.
  • Monitoring your triggers. Try to keep a running list of certain situations or activities that often accompany your attacks. This can help you avoid them in the future.
  • Carrying an extra inhaler. Always keep an extra inhaler with you for emergencies. If youre traveling, bring some extra medication with you.
  • Talking to friends and family. Tell those close to you how to recognize the signs of a severe asthma attack and why they should take you to a hospital if they notice them. People who dont have asthma might not realize how serious your condition is.

Prognosis Of Patients In Status Asthmaticus

Status asthmaticus carries a significant mortality, ranging between 1 and 10% . Among patients in status asthmaticus admitted to an intensive care unit, between 10 and 30% required mechanical ventilation . In recent years the mortality rate of patients in status asthmaticus requiring mechanical ventilation has decreased significantly . This decrease may reflect earlier diagnosis, aggressive medical treatment, and improvements in mechanical ventilation . Death from asthma in mechanically ventilated patients appears to be further decreased after the application of the ‘permissive hypercapnia technique’.

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Pathophysiology Of Asthma And Acute Asthma Exacerbations: Brief Overview

Figure 1.

Major immunopahtologic processes that take place in the bronchial airways of patients with asthma. Please see the text for detailed description. FcRI, high-affinity receptor for IgE IFN, interferon- TCR, T-cell receptor TNF, tumour-necrosis factor. Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Immunology. Stephen T. Holgate and Riccardo Polosa. Treatment strategies for allergy and asthma. Vol. 8:Page 220, Copyright 2008.

The most common cause of acute asthma exacerbation in both adults and children, but more in children, is viral respiratory tract infections. Viruses may be responsible for up to 80% of wheezing episodes in children and 50-75% of episodes in adults . Many viruses can cause exacerbation of asthma symptoms, the most important and most common is rhinovirus . Respiratory syncycial virus and influenza virus also cause significant proportion of exacerbations. The pathology of virally induced asthma exacerbation is more related to the airway epithelial cells which, in response to infection secret chemokines like IL-8 and CCL-5 that can attract inflammatory cells including neutrophils and lymphocytes and augment allergic inflammation . This finding is supported by epidemiological observations that allergen sensitization and respiratory viral infections can synergize to cause asthma exacerbation . Children who are atopic are more likely to have virally induced wheezing and respiratory distress than non-atopic children .

Changing Concepts In Asthma Diagnosis Severity Assessment And Treatment And Their Effects On Asthma Progression And Mortality

The first guidelines on asthma diagnosis and management were published in the late 1980s . The development of these documents was stimulated by an increase in asthma-related mortality in several countries , and a marked increase in asthma prevalence in many countries in the 1970s and 1980s . These were consensus statements, rather than formal evidence-based clinical practice guidelines, but all identified the need to establish the diagnosis of asthma using objective criteria to document variable lung function, which has not changed over time, and recommended treatment options based on the perceived severity of the disease. The objectives of treatment were to improve symptom control and lung function. The importance of airway inflammation in asthma pathogenesis had already been identified , but the early documents did not emphasise the benefits of anti-inflammatory treatments, and as a result medications that rapidly improved symptoms and lung function, particularly inhaled 2-agonists, were the focus of treatment, especially for patients with mild-to-moderate asthma.

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Impact Of Ics On Long

In the majority of individuals with asthma, treatment with ICS improves symptoms and lung function, reduces the frequency of exacerbations, and reduces airway inflammation . In addition, the very earliest studies of the efficacy of ICSs in asthma demonstrated their ability to reduce or eliminate the need for OCSs as a maintenance treatment . Furthermore, registry studies have shown that even low doses of ICS reduce the risk of severe asthma exacerbations and death from asthma . The ability of ICS to reduce the risk of severe exacerbations can even be seen when ICSs and rapid-onset inhaled 2-agonists, delivered from the same inhaler, are only used as a reliever treatment .

Observational, nonrandomised studies of both children and adults followed in asthma clinics , and studies of adults with asthma from the general population , have suggested that ICS treatment may have beneficial effects on the course of lung function. However, this has been very difficult to prove in an RCT, since in excess of 3years of observation are needed to draw conclusions about long-term changes in FEV1, due to the combination of considerable measurement error and a very modest age-related annual FEV1 decline . In addition, randomisation of individuals with even mild asthma to placebo maintenance therapy may result in substantial withdrawal during such a study due to inadequately controlled symptoms and the occurrence of exacerbations.

Pearls And Other Issues

Asthma Symptoms and Treatment – Explained under 4 minutes.

The incidence and prevalence of severe asthma are increasing in both adults and children. Such episodes may progress to a status of progressive respiratory failure refractory to standard therapeutic measures. Early recognition of such severe episodes, based on clinical signs, lab data, and follow-up evaluations at close intervals, can be life-saving. An initial aggressive treatment trial of beta-agonists, corticosteroids, and anticholinergics has to be tried, followed by adjunct measures, which may not be based on robust guidelines but evidence. Although initially avoided, mechanical ventilation is indicated for certain specific situations, including altering consciousness, respiratory fatigue, or cardiopulmonary arrest. There have been recent advances in ventilation strategies to protect against barotrauma, alveolar trauma, and neuromyopathy.

Finally, once resolved, attention needs to be paid to avoiding future severe episodes for which the patient carries an increased risk.

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Management Of Patients Admitted To The Hospital: Wards And Icu Care

Careful consideration must be given to the level of care required when a patient with an exacerbation of asthma is admitted to the hospital. In general, guidelines suggest that patients should be admitted for observation and further treatment if the pretreatment FEV1 or PEF is < 25% of predicted or of personal best or if the post-treatment values are < 40% after emergency department treatment. Typically, patients who demonstrate a poor response to therapy , persistent or unresponsive hypercapnia, altered mental status, hypotension, or have significant comorbid conditions should be admitted to the ICU.

Although many patients maintain good oxygen saturations despite severe airway obstruction, some patients develop small airway mucus plugging even after the PEF/FEV1 normalize. Guidelines suggest that oxygen should be administered via nasal cannula or oronasal mask to maintain an arterial oxygen saturation of 9395% in adults and 9498% in children. In severe exacerbations, low-flow oxygen therapy by titrating the saturation to 9395% was associated with better physiological outcomes than with high-flow 100% oxygen therapy.

Asthma Control Severity And Unresponsiveness

For the majority of patients with asthma, control can be achieved with conventional therapy, and indeed some patients enjoy complete freedom from asthma symptoms using such therapy.10,11 Unfortunately, surveys in Canada and elsewhere have shown that many patients, perhaps the majority, fail to achieve adequate disease control.4,12 It is widely believed that this is not a consequence of intrinsically severe asthma, but rather of inadequate management, poor patient education or a combination of these 2 factors.4,13

A separate issue from symptom control is the definition of asthma severity.6,14 Frequent symptoms and exacerbations are not synonymous with severe disease. Patients with mild disease may have frequent symptoms or exacerbations if adequate maintenance therapy has not been prescribed or they are not taking their prescribed medications. Conversely, patients with severe disease may be free of symptoms and exacerbations if they have been given appropriate therapy. A simple guide to a patients degree of asthma severity is the minimum amount of medication that he or she needs to maintain disease control.15

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