The role of bronchoscopy in wheezy children
T. Nicolai
Univ. Kinderklinik München im Dr. von Haunerschen Kinderspital
Address for correspondence:
Dr. T. Nicolai
Univ. Kinderklinik
Lindwurmstr.4
80337 München
Germany
Tel ++498951602841
Fax ++498951604409
Email tnicolai@med.uni-muenchen.de
Abstract
Introduction
Recurrent or severe wheeze is a common diagnostic and therapeutic problem particularly in young
children with respiratory symptoms (For the purpose of this discussion, we shall not consider the
symptom of inspiratory stridor, although sometimes this is referred to as inspiratory wheeze).
Diagnostic issues may include the search for “mechanical” causes of wheeze such as structural airway
narrowing, tracheobronchomalacia, compression by intrathoracic structures such as vessels, heart,
cysts, tumors or obstruction by a foreign body. If none of these differential diagnoses is likely, it
would be helpful to determine whether the child belongs to one of the subgroup of recurrent or
persistent wheeze phenotypes that are currently recognized: transient wheeze (which is associated with
young maternal age and maternal smoking and will disappear after the first two years of life), viral
associated wheeze (which lasts into school age but usually resolves then) and early manifestations of
asthma which may persist. Therapy would clearly be different for a child belonging to one of the first
two phenotypes compared to the last, but symptoms are identical and it only becomes clear in
retrospect to which diagnostic group an individual patient belongs. Currently, no clinical parameter
allow us to discern the patients early in their disease.
The use of the flexible endoscope in investigating pediatric respiratory problems has become routine.
The investigational use of bronchoscopy and bronchoalveolar lavage (BAL) has led to significant
insights into various pulmonary disease processes. Bronchoscopy in children has proved to be
associated with little risk when performed in experienced centers (1), but other reports comparing
multicenter data and sick children have shown that a few patients may still experience significant
problems during the procedure, particularly if they had respiratory difficulties before the examination
(2). Transient hypoxia was reported in 23% and one of 30 patients experienced a bradycardic event
when children with wheeze underwent bronchoscopy and BAL (3), while a more recent study on
bronchoscopy in 113 similar children reported hypoxic events in 6% of procedures (4).
It is the purpose of this paper to discuss the place and utility of fiberoptic bronchoscopy in addressing
the diagnostic issues outlined above.
Bronchoscopy as a tool for differential diagnosis
If there is an overwhelming likelihood of a diagnosis of asthma (e.g. both parents severe asthmatics
and atopic dermatitis in the child) together with a typical chest auscultation and a clinical
improvement after inhalation of betamimetics, no bronchoscopy is needed. If other causes of wheeze
such as CF have been ruled out or are unlikely, or if the obstruction is unilateral and the patient has
severe wheeze with a “tracheal” quality to it and /or the wheezing sound is associated with stridor, a
bronchoscopy is usually warranted. Cardiac ultrasound, a chest x-ray including the laryngeal region, a
CT scan (sometimes) and (mostly in older children) a lung function test are usually done before the
endoscopy. Foreign bodies, tracheobronchial malacia, tracheal stenosis, vascular malformations
(double aortic arch, pulmonary sling) and endobronchial tumors (carcinoid, mucoepideroid carcinoma,
hemangioma, inflammatory pseudotumor) compromising the airway can thereby be identified. A study
investigating 47 children with severe recurrent wheeze found structural abnormalities in 36% of
bronchoscopies, one foreign body and visible inflammation in 27% (5).
Tracheomalacia as a cause of wheeze is common after oesophageal atresia and some malformation
syndromes but can occur in isolation. Other diagnostic options such as a lateral chest X-ray, CT scan,
and MRI, will often not give clear enough information, but bronchoscopy will allow to make a
definite diagnosis. While collapse of the tracheal lumen (usually most prominent at the point where the
truncus brachiocephalicus crosses the trachea) during quiet spontaneous breathing is abnormal, the
same could be seen in a normal trachea during coughing or with active expiratory effort. One study
found that, in contrast to tracheomalacia, the cross sectional area of a normal trachea decreased < 25%
from its maximum during spontaneous breathing, and the ratio between cartilage and pars
membranacea was lower in tracheomalacia. However, this study used a clinical diagnosis of
tracheobronchomalacia as the gold standard and analyzed only seven cases and eight controls, which
makes it difficult to generalize the findings. Normal values from larger number of children without
tracheobronchomalacia for the relative contribution of cartilage and pars membranacea to the tracheal
circumference are clearly needed. Directly measuring the stability of children’s airways during
bronchoscopy (e.g. transmural pressures and corresponding airway size) is impractical in clinical
routine and normal values have not been established. Usually, the stability of the airway during
bronchoscopy is determined visually as described above. However, this method is not without pitfalls
for technical reasons: if the bronchoscope is large compared to the airway (e.g. in infants), it will
increase airway resistance proximal to the area visualized. Therefore, dyspnoea and active expiration
may ensue, leading to a false diagnosis of tracheobronchomalacia, or to inadvertent PEEP and
expiratory distension of the airway (masking tracheobronchomalacia). It is therefore important to
tailor sedation / anaesthesia exactly to assure quiet breathing with a sufficient tidal volume and flow to
allow a confident diagnosis of this entity. However, once the diagnosis is ascertained, unnecessary
therapies such as inhaled steroids or beta-mimetics can be stopped, and in severe cases surgical
interventions such as aortotruncopexy may be considered.
The diagnostic value of bronchoscopy in suspected chronic aspiration or reflux associated respiratory
symptoms and wheeze is less clear. In infants, endoscopy (sometimes combined with
oesophagoscopy) may be useful if aspiration is strongly suspected. If a lateral chest X-ray in the prone
position with contrast filling of the esophagus has suggested an isolated tracheoeosophageal fistula or
laryngeal aspiration, bronchoscopy is useful to thread a thin catheter through the fistula preoperatively
to simplify its location, or to identify a laryngeal cleft. If reflux/aspiration is suspected, bronchoscopy
can identify dorsal laryngitis and tracheobronchitis making it more likely that the wheeze may be
caused by this mechanism. A trial with a proton pump inhibitor then usually clarifies its contribution
to the clinical picture.
Bronchoscopy and BAL analysis and bronchial biopsies
A retrospective case series investigated 30 young children with recurrent wheeze poorly responsive to
bronchodilators, who mostly had been tentatively labeled asthmatic, with bronchoscopy and BAL (3).
While tracheomalacia was found in 12 and treated with aortopexy in one, the findings for the BAL
culture and cytology are more difficult to interpret. Bacteria (11%) and viruses (33%) were isolated,
and abnormal cell differential was reported in 41%. However, it was not reported how the treatment
was varied depending on the BAL results and what change in clinical outcome was achieved on this
basis.
While BAL and the lipid laden macrophage index (LLM) have been advocated as a useful indicator
for chronic aspiration, others have found considerable overlap with various bronchopulmonary
disorders or normal children making the LLM almost useless. It appears that the lipids in the lipid
laden macrophages represent endogenous lipids from inflammatory cells rather than exogenous
aspirated material. One study investigated children < 18 months with recurrent wheeze which was
poorly responsive to bronchodilators (3), and while four patients with proven reflux had an elevated
LLM, two of these also had adenoviruses cultured from the airways, making the LLM findings
difficult to interpret. Increases in this indicator have also been found after lipid infusions and in a child
with veno-occlusive disease of the lung.
One study (5) investigating 47 highly selected children with severe chronic wheeze found
inflammation in BAL samples in 65%, and fat laden macrophages in 75%. A bronchial mucosal
biopsy was also done in this series, and basement membrane thickening (29%) and eosinophilic
inflammation (44%) were interpreted as characteristics for asthma. Still, it was not reported whether
these interpretations and the therapeutic decisions resting on them resulted in better clinical
management for the individual patients, and whether the diagnostic groups defined in the paper
represent the different prognostic wheeze phenotypes mentioned above. The clinical utility and
possible incremental diagnostic benefit from BAL and bronchial biopsy in this situation and for less
severe wheeze remains an important field of research.
Studies using sophisticated BAL cytology and inflammatory mediator measurements to investigate
pathomechanisms of chronic or recurrent airway inflammation have shown various abnormalities in
these patients. Unfortunately, at the moment it seems not yet possible to confidently predict whether
a given patient has transient wheeze, wheeze with viral infection or incipient asthma from this kind of
BAL derived measurements. Therefore, the routine use of BAL in wheeze outside of clinical studies
seems not necessary.
Special circumstances
For patients who develop wheeze with certain preexisting conditions (such as bone marrow
transplantation, lung transplantation or immunodeficiency) bronchoscopy, BAL and even
transbronchial biopsy may be indicated to search for unexpected pathogens, graft versus host reactions
or rejection. Some children who have undergone a Fontan-type repair of a cardiac defect may develop
bronchial casts (plastic bronchitis). If these cause life threatening airway obstruction and do not react
to conservative therapy such as withholding oral long chain fatty acids, attempts to dissolve the casts
through urokinase inhalation etc., bronchoscopic removal of the obstructing casts may be life saving.
Conclusions
In our experience, a bronchoscopy is justified in children with severe or persistent chronic wheeze
when careful investigations, as outlined above, have failed to arrive at a diagnosis and/or therapeutic
trials have not improved symptoms, or if there is an unexplained worsening of symptoms. In many
cases, a definite morphological diagnosis can be made and unnecessary therapy can be stopped. The
addition of BAL and bronchial biopsy in order to better characterize the remaining cases is currently
an important tool for research and may be indicated clinically in selected cases.
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