Anti-inflammatory Effect of Nocturnal NIPPV on Acute Asthma

RESEARCH QUESTION What is the effect of non invasive positive pressure ventilation (NIPPV) on systemic inflammation in patients with asthma attacks?

JUSTIFICATION Asthma is a global public health problem and one of the primary causes of care at the National Institute of Respiratory Diseases in Mexico; when presented as a crisis is a serious condition that puts the life of the patient at risk; in vitro and in vivo studies have shown that the application of chronic airway distention using non-invasive mechanical ventilation produces a reduction in bronchial hyperreactivity in patients with asthma and may have a positive effect on the treatment of this condition independent of its effects on ventilation in the presence of acute respiratory failure.

HYPOTHESIS The use of NIPPV will improve systemic inflammation assessed by C reactive protein (CRP) in patients with severe asthmatic crisis.

OBJECTIVES

Main Objective:

To assess the effect of NIPPV on systemic inflammation measure through C reactive protein in acute asthma

Secondary objectives:

• - To assess the effect of NIPPV on the days of hospital stay in patients with asthma attacks.
• - To evaluate adherence to NIPPV in patients with asthma attacks.
• - To evaluate the effect of NIPPV on PaO2, PaCO2 and SpO2 in patients with asthma attacks.
• - To evaluate the effect of NIPPV on FEV1 and Exhaled fraction of nitric oxide in patients with asthma attacks.
• - To evaluate the effect of NIPPV on serum levels of interleukin (IL)-4, IL-5, IL-13 and IL-17 in patients with asthma attacks.
• - To assess the effect of NIPPV on total eosinophil count and Immunoglobulin (Ig) E level in patients with asthma attacks.

MATERIALS AND METHODS

• Design: A prospective, longitudinal, comparative, parallel group study will be conducted; it was approved by the Science and Bioethics Committees of the National Institute of Respiratory Diseases Mexico with the code C34-14. In all cases, informed consent will be requested.
• Place: It will be carried out in the emergency and hospitalization service of the National Institute of Respiratory Diseases "Ismael Cosío Villegas" at Mexico city.
• - Procedures:

• Clinical history.
• Chest X-ray.
• Berlin Questionnaire. The Berlin questionnaire is a self-administered questionnaire validated in Spanish to establish the risk of obstructive sleep apnea.
• Arterial gasometry.
• Blood cell count.
• Ultrasensitive C-reactive protein.
• Determination of IgE.
• Spirometry and Exhaled fraction of nitric oxide according to international guidelines.
• - Intervention: Patients included will be randomized to receive, 4 nights of noninvasive nocturnal positive pressure ventilation with an S Bilevel device with a 12 cmH2O inspiratory pressure and a 4 cmH2O expiratory pressure or a 4 cmH2O Continuous Positive Airway Pressure (CPAP), as a control group.

The equipment will be placed at night ad libitum and retired the following day in the morning, in all cases a VPAP ST S8 RESMED will be used. If the patient needs to increase inspired oxygen fraction it will be performed with nasal tips during the day and a distal oxygen connector at night. In all cases a nasal mask will be used.

Blood gasometry, blood cell count, CRP, serum IL-4, IL-5, IL-13, IL-17 and IgE, Spirometry and Exhaled fraction of nitric oxide will be repeated at day 4.

• - Data Analysis A convenience sample of 20 patients was established. A balanced randomization will be performed. The variables were summarized according to their type and distribution. The comparison of dichotomous variables will be performed using Fisher's Exact test. The comparison of independent continuous variables will be carried out with U of Mann Whitney and the related variables will be analyzed with Wilcoxon Related Ranks Test.

Inclusion criteria

• Diagnosis of asthma, performed by a physician, with spirometry and stable treatment for at least 3 previous months.
• Severe asthma crisis and hospitalization requirement of at least 4 days.

Exclusion criteria

• Life-threatening crisis.
• Requirement of Invasive or Non-Invasive Mechanical Ventilation.
• High risk for Obstructive Sleep Apnea (measured through the Berlin questionnaire).
• Active smoking.
• Another chronic lung disease other than asthma.
• Pneumonia (defined by the presence of an opacity of the lung parenchyma on a chest x-ray).
• Ischemic heart disease.
• Uncontrolled systemic arterial hypertension.