Obesity and asthma: effect of bariatric surgery on lung function, inflammation and quality of life.

The prevalence of obesity has dramatically increased in the Netherlands over
the last years. In 7 years, 10% of the population will be obese (BMI > 30).
Epidemiological studies have shown that obesity increases the risk of asthma
and is related to the severity of asthma. Several mechanisms have been
mentioned. In obesity, a reduction in lung volume takes place which also has
consequences for airway resistance. In obesity, systemic inflammation is
present with a possible effect on the airways. Also gastro-oesophageal reflux
symptoms are often prevalent in obesity and could be a possible cause of airway
pathology. Finally, links between obesity and asthma could partly be explained
by a common genetic background. Bariatric surgery has a beneficial effect on
symptoms and lung function in obese patients with asthma. The problem with
previous intervention studies is the relative small size and the lack of
control groups. In addition, it is unclear whether the observed effect of
weight reduction on asthma symptoms is the result of improvement of
pathophysiological parameters or a reduction of systemic inflammation, or both.

The aim of the study is first to develop knowledge concerning underlying
mechanisms that can explain the relationship between obesity and asthma.

Eighty morbid obese patients (40 with asthma and 40 without asthma) will prior
to and half-yearly after bariatric surgery visit the pulmonary department and
undergo spirometry, symptom scores, nitric oxide measurement (FeNO) and blood
sampling. During surgery, bronchial and visceral biopsies will be taken from
the subjects. Bronchoscopy will be repeated 1 year after operation. Expression
of inflammatory mediators, such as tumor necrosis factor alpha (TNF-α), IL-6,
leptin en adiponectin will be assessed in biopsy material and blood. A
non-intervention group of 20 obese asthmatics will serve as controls. They will
folow the same procedures as the intervention group except for bronchoscopy.
The total follow-up of the study will be one year after surgery.

Patients will have no personal benefit from the study. The study comprises six
visits (see study design paragraph). The first visit is already standard
practice. Most procedures are non-invasive (e.g. spirometry, FeNO measurement,
symptom score and quality of life assessment). Two procedures are invasive and
may be potential harmful. First, during the visits blood samples will be taken
on three occasions (60 ml). This may lead to bruises, which will resolve
spontaneously. Second, on visit 3 and 7, bronchoscopies will be performed. The
first bronchoscopy will be performed after intubation of the patients. This is
regarded as a safe procedure. Since the patients are deeply sedated, they will
not be aware of the procedure. The second bronchoscopy will take place 1 year
after bariatric surgery. By that time, the expected weight reduction will be
30%, resulting in a substantially lower chance of complications. Several
bronchial biopsies (max. 6) will be taken from the central bronchial mucosa.
This may cause some minor bleeding, which will often stop spontaneously or may
need intervention by cold water installation or xylomethazoline. The risk of
major bleeding or pneumothorax after taking central bronchial biopsies is
extremely low. Visceral fat biopsies will be collected during laparoscopy and
are not considered to add additional risk to the operation.