Discussion
PCD is a lifelong disease that can promote occurrence of recurrent
airway infections that finally resulted in bronchiectasis and declining
lung function that, in turn, support
development of respiratory
infections and perpetuate a vicious cycle of disease. Interrupting this
vicious cycle is vital in order to delay disease progression. In fact,
results of several studies have shown that AZM treatment of patients
with CF and non-CF bronchiectasis for 3-6 months improved lung function
and nutritional status, while also reducing C-reactive protein levels,
pulmonary exacerbations and hospitalization rates[7-10], but only one multicenter phase 3 trial
study was performed that showed similar results included both pediatric
and adult PCD patients [14]. Here, we
retrospectively studied a school-age pediatric population with a mean
age at baseline of 8.0 years and a mean age at follow-up of 11.03 years,
parts of baseline data had been reported in previous study[15]. Our results revealed that pediatric PCD
patients with long-term AZM use experienced significantly fewer
respiratory infections than those who had not taken AZM, as observed in
the previous study [14].
Azithromycin is currently widely used in chronic respiratory diseases
including PCD [16], due to its ability to
alleviate both infection and inflammation. More specifically, AZM plays
an anti-infective role by inhibiting synthesis of bacterial proteins
that can interfere with bacterial biofilm generation and production of
other virulence factors [17]. Concurrently, AZM
plays an anti-inflammatory role by inhibiting host production of IL-8
and tumor necrosis factor-α (TNF-α) [18-19].
Notably, the decreased frequency of respiratory infections in the
AZM-treated group as compared to the control group may be related to
relatively reduced daily sputum volume associated with AZM treatment
effects on mucus properties and mucus production[20]. In addition, our results also revealed that
PCD patients who received long-term AZM therapy exhibited less exercise
intolerance as compared to control group. Which indicated that a history
of long-term AZM use administered three times per week reduced the
frequencies of respiratory infection-triggered inpatient and/or
outpatient doctor visits, while also improving school attendance and
overall quality of life.
Studies have shown that early in life, impairment of PCD patient lung
function begins and increases with age, with magnitudes of PCD
disease-induced effects on FEV1 and FVC values eventually resembling
those reported in studies of CF patients [21-22].
However, few studies have investigated macrolide antibiotic treatment
effects on FEV1 values of non-CF bronchiectasis produced conflicting
results [23-25], with only one of the studies
indicating improvement of FEV1 after treatment[23]. In this study, lung function varied widely
among our patients and the mean follow-up time was 3.1 years and longest
follow-up duration was 9.4 years. Importantly, baseline
FEF25-75 of patients in the AZM-treated group were lower
than that in corresponding control group. Moreover, AZM-treated group
lung function improved slightly more than that of the control group,
although the intergroup difference was of no apparent difference, due to
small numbers of patients in both groups with both baseline and
follow-up pulmonary function test results. Ultimately, the results
collectively suggest that regularly long term AZM use may stabilized
FEV1, FVC, and FEF25-75 in patients with poor lung
function or more severe disease resulting from frequent infections.
In fact, that lung spirometry is less sensitive than high-resolution
computed tomography (HRCT) at detecting functional and structural lung
damage induced by PCD disease [26]. Thus, CT scans
were used here to assess lung damage in our PCD patient cohort. Results
of this study, which were of no statistically significant between-group
differences at baseline, revealed that about 90% of patients in the
AZM-treated group exhibited signs of stable or improved lung function as
compared to about 75% of that in control group patients. However, this
change did not differ apparently between the two groups which need to be
confirmed by more detailed and rigorously designed studies due to the
evaluation complexity of imaging changes.
Importantly, Goutaki M et al investigated a large group of over 3000 PCD
patients, which indicated that both growth and nutrition are affected
adversely in PCD patients from early life with delayed diagnosis[28]. However, other studies showed preschool
referral to a PCD center was not associated with better BMI[29]. Our results revealed that BMI was a little
lower in both groups at baseline which may be associated with late
diagnosis in this cohort, while the mean heights were in normal range.
Notably, although the average follow-up duration of the AZM-treated
group was shorter than that of the control group, the percent increase
in height of the AZM-treated group was slightly greater than that of
controls, but the intergroup difference was of no statistical
significance. Indeed, at first measurement, most PCD patients in this
study were of normal height and weight. Thus, these indicators would not
likely increase further with AZM treatment during follow-up.
The most common adverse reactions associated with AZM treatment which
were observed in this study were that occasional and mild
gastrointestinal reactions experienced only in three patients who
received regular AZM treatment. Importantly, such reactions improved
after patients adjusting the timing of AZM administration. Although
hearing decrements were observed to be more common in the azithromycin
group in a 12-month RCT in patients with chronic obstructive pulmonary
disease [30], no serious adverse reactions, such
as ototoxicity and cardiotoxicity, were observed.
A limitation of this retrospective study that lung function tests, chest
CT scans, and sputum cultures were not regularly conducted during
follow-up duration, which indicate that inadequate patient education and
inconsistencies of disease management was exist in China. In the future,
establishment of PCD follow-up treatment programs at medical research
centers with standardized prospective collection of data related to
characteristics and factors associated with PCD phenotypes may help to
provide more scientifically based and comprehensive disease management
evidence.