An assessment of nutritional deficiencies in patients with primary antibody deficiency and bronchiectasis.

Primary antibody deficiencies (PAD) are the most frequently encountered immune
deficiency disorders in men. Affected individuals suffer from an increased
susceptibility for infections, caused by either a shortage or a loss of
function of antibodies (immunoglobulins). A wide range of primary antibody
deficiency syndromes exists, the most prevalent of which are selective IgA
deficiency (1:600) and common variable immune deficiency (1:25.000).
Substantial morbidity and mortality arises from the different complications of
PAD, which may vary from granulomatous or lymphoproliferative disorder in CVID
to severe opportunistic infections or auto-immunity in Good*s syndrome
(thymoma-associated hypogammaglobulinemia). However, the most frequently
encountered complications of PAD are various forms of respiratory disease, most
often bronchiectasis [1]. Bronchiectasis, which has been found to be present in
roughly a quarter of patients with PAD, is defined by widening of the large and
medium size bronchi as a result of increased burden of infection and
concomitant inflammation. Key symptoms in bronchiectasis are recurrent airway
infections and chronic symptoms such as dyspnoea and a debilitating productive
cough [2].
Immune globulin administration has been standard of care in most PAD for over
25 years now and has induced a significant improvement of morbidity and
mortality due to a reduction in the incidence of acute infections in patients
with PAD [3].
Concomitant bronchiectasis, when symptomatic, is usually treated with measures
to improve sputum evacuation such as dedicated physiotherapy and hypertonic
saline inhalations. In addition, patients who experience frequent exacerbations
despite these measures may be treated with maintenance antibiotics, most
frequently macrolides [4].
In many cases, these treatment modalities reduce the occurrence of new
infections and alleviate chronic symptoms in patients with a PAD and
bronchiectasis. However, a large subset of patients keeps having frequent
infectious exacerbations and/or chronic pulmonary symptoms, despite adequate
treatment. In addition, some of the above mentioned measures have important
downsides which makes them unattractive for application in some patient groups.
For instance, macrolides were noted to cause side effects in almost half of
patients treated with azithromycin in a randomized clinical trial [4]. Apart
from this, widespread use of macrolide antibiotics is at itself not desirable,
because of its tendency to induce macrolide resistance on a population level.
This problem may become more urgent in the near future, because the recent
publication of randomized trials showing a favourable effect of long term
macrolide treatment, not only in bronchiectasis, but also in asthma and COPD,
prompted many clinicians to prescribe long term antibiotics in patients with
frequent exacerbations.

The above provides arguments for a search for new treatment modalities and for
measures which further strengthen the immune system in order to prevent
infections and other symptoms in patients with PAD and bronchiectasis.

In a decade where nutrition and food gets more and more attention, exploring
the role of diet and deficiencies appears a logical step forward. Nutritional
interventions may have the ability to reduce inflammation and as such to reduce
the frequency of infectious exacerbations. In addition, most dietary measures
are cheap and feasible in most clinical and outpatient settings.

For the immune system to function efficiently, adequate dietary intake is
required. This interaction between dietary habits and immunity has been well
recognized for decades [5;6], . Nutritional deficiencies are known to cause
increased susceptibility to infections, by interacting with innate and cellular
immunity [7;8].
In turn, (chronic) infections may be the cause of nutritional deficiencies by
reducing dietary intake in general or increased turnover of nutrients [9].
PAD patients, suffering from recurrent infections, will therefore be
specifically at risk both to develop nutritional deficiencies and to suffer
from the increased susceptibility for infections caused by deficiencies.

Several nutrients have been investigated for their effect on the immune system,
the most familiar of which is vitamin C, which was found to reduce systemic
inflammation in healthy volunteers and to play a role in facilitating cure in
common cold and upper airway infections [10;11]. But also other nutrients, such
as vitamin A, B6, B12, folic acid and selenium, iron and zinc were found to
improve immune function through various pathways [6].
Interventional studies in this area are scarce, only reflecting the need for
more research in this specific field. However, the available evidence so far
shows a consistent trend to improved immune function following suppletion of
vitamins, minerals and/or trace elements in health volunteers and specific
patient groups [12].

Primary Objective:
To assess dietary intake of macro- and micronutrients, body composition and
serum levels of nutrients in patients with primary antibody deficiency and
bronchiectasis.

Secondary Objective(s):
- To evaluate the correlation between disease severity, dietary intake, body
composition and serum levels of micro- and macronutrients.

This is an observational pilot study in 25 patients with a PAD and
bronchiectasis, visiting both the outpatient department for primary immune
disorders of the department of immunology and the pulmonology outpatient
clinic.

For each patient, one study visit will be scheduled, at which they will be seen
by a dietician for evaluation of dietary intake and calculations of recommend
intake for macro- and micronutrients. In addition, body composition will be
estimated using bioelectrical impedance analysis (BIA). At the same occasion,
blood samples will be taken in order to test for levels of micronutrients and
each patient will be asked to fill out 3 questionnaires on QoL and symptoms
(LRTI-VAS, CVID-QoL and QOL-B) (see attachment).

Baseline characteristics of all participants will be collected by chart review

limited to the risks involved in venous blood sampling and regarded as
negligible.