Subjective Sleep Quality and Sleep Disorders in Patients With Severe Asthma
Subjective Sleep Quality and Sleep Disorders in Patients With Severe Asthma
Bronchial asthma is characterized by the presence of symptoms that vary over time and of
 severity. Asthma symptoms tend to worsen at night and in the early hours of the morning, and
 the presence of nocturnal symptoms is an important indicator of therapeutic intervention in
 order to control the severity of the disease. Aim of the study is to investigate sleep
 disorders and quality, as well as and depressive and anxiety symptoms in patients affected by
 severe asthma before and after 6 months of treatment with monoclonal therapy. An
 observational, cohort, prospective, monocentric study will be conducted to evaluate
 subjective quality of sleep at baseline and post monoclonal treatment.
Rationale

 Bronchial asthma is a heterogeneous and highly prevalent disease; moreover, it represents one
 of the main cost of the Italian National Health Care System. According to international
 guidelines, asthma is characterized by the presence of symptoms such as wheezing, dyspnoea,
 chest tightness and / or cough, and limitation of expiratory air flow, that vary over time
 and of severity.

 The main therapy consists of the use of inhaled corticosteroids in order to reduce airway
 inflammation; however, in conditions characterized by frequent exacerbations, patients take
 oral corticosteroids (OCS) cyclically or chronically to control their symptoms. Asthma
 symptoms tend to worsen at night and in the early hours of the morning, and the presence of
 nocturnal symptoms is an important indicator of therapeutic intervention in order to control
 the severity of the disease.

 Several studies have shown that nocturnal symptoms, such as cough and dyspnoea, are
 associated with circadian oscillations of airway inflammation and physiological variables,
 with consequent air flow limitation of and bronchial hyperreactivity. Moreover, it is known
 that patients receiving OCS are subjected to significant alterations of the
 hypothalamic-pituitary-adrenergic axis function, therefore the assumption of these drugs
 could cause a modification of the circadian rhythm.

 Since sleep fragmentation that accompanies the worsening of nocturnal asthmatic symptoms is
 probably caused by the degree of severity of nocturnal bronchoconstriction, it is possible
 that severe asthmatic patients have greater bronchoconstriction and therefore more disturbed
 sleep.

 Subjects with severe asthma, the 5-10% of the total asthmatic population, report symptoms
 that persist despite inhalation therapy, and have many exacerbations, Emergency Room access
 or hospitalizations.

 These patients use systemic steroids at least twice a year due to asthmatic exacerbations and
 / or continuous therapy with systemic steroids for at least 6 consecutive months, with the
 development of side effects such as high blood pressure, overweight, meta-steroid diabetes
 and osteoporosis.

 In the last ten years, the availability of alternative therapies such as monoclonal
 antibodies, which block the inflammatory cascade at different levels (Anti Immunoglobulin E,
 Anti interleukin-5 (II-5)e anti receptor Il-5) has allowed to reduce the dosage of steroid
 therapy up to its complete suspension.

 Obstructive Sleep Apnoea (OSA) is one of the most common asthma comorbidities, especially
 severe, affecting about 26% of patients. When evaluated with polysomnography, the prevalence
 of OSA is equal to 88% in patients with severe asthma and 58% in those with moderate asthma.

 It seems that OSA could contribute to asthma exacerbations, to diurnal and nocturnal symptoms
 and to the scarce quality of life; it also seems to modulate airway inflammation and
 remodeling. Asthmatic patients with OSA show a greater decline in Forced Expiratory Volume in
 the first second (FEV1) over time than non-OSA, and Continuous Positive Airways Pressure
 (CPAP) treatment seems to slow down this deterioration. Serrano Pariente et al. have
 demonstrated that 6 months CPAP treatment improves the outcomes of Asthma in patients with
 moderate OSA. Finally, a recent study has shown that patients with poorly controlled asthma
 tend to have worse sleep quality and greater diurnal sleepiness. The same study has
 demonstrated a higher prevalence of depressive symptoms in female patients with poorly
 controlled asthma.

 Aim of the study is to investigate sleep disorders and quality, as well as and depressive and
 anxiety symptoms in patients affected by severe asthma before and after 6 months of treatment
 with monoclonal therapy.

 Primary outcome is to evaluate subjective quality of sleep at baseline and post treatment.

 Secondary outcomes are: to verify pre and post treatment: the presence of insomnia,
 respiratory disorders, circadian rhythm disorders, diurnal sleepiness or anxiety and
 depression symptoms.

 Inclusion criteria:

 -  Diagnosis of severe persistent asthma

 -  Systemic steroids treatment for at least 6 months and/or ≥2 exacerbations in the last
 year

 -  Need to initiate monoclonal antibody therapy according to guidelines

 -  Age ≥18 years

 -  Signed Informed consent

 -  Patients able to collaborate in the required procedures

 Exclusion criteria:

 Diagnosis of cognitive impairment Study Design An observational, cohort, prospective,
 monocentric study will be conducted. Patients will be enrolled c/o the Pneumology Division of
 the Clinical and Scientific Institute Maugeri of Tradate.

 Data will be collected at baseline (T0) and after 6 months of therapy with one monoclonal
 antibody (omalizumab, mepolizumab or benralizumab) (T6).
Inclusion Criteria:

 -  Diagnosis of severe persistent asthma

 -  Systemic steroids treatment for at least 6 months and/or ≥2 exacerbations in the last
 year

 -  Need to initiate monoclonal antibody therapy according to guidelines

 -  Age ≥18 years

 -  Signed Informed consent

 -  Patients able to collaborate in the required procedures

 Exclusion Criteria:

 -  Diagnosis of cognitive impairment