Biomedical Engineering Reference
In-Depth Information
asthma symptoms and airway hyperresponsiveness are associated with
pathological abnormalities in central airways, whereas lung parenchyma
is unchanged, at least in baseline conditions (19,38). In the central airways
of asthmatics, the characteristics pathological abnormalities are: (1)
an increased number of mononuclear cells, particularly T-lymphocytes
of the CD4
รพ
Th2 type, associated in most cases with eosinophils and
mast cells in the airway mucosa and in the airway fluid, (2) damaged airway
epithelium, and (3) increased thickness of the lamina reticularis of the base-
ment membrane. The contribution of these pathological abnormalities to
symptoms of asthma and airway hyperresponsiveness remains unclear.
The peripheral airways of asthmatics have been examined only in one
study that showed substantially similar, although more severe, infiltration
by T cells and eosinophils (Ref. 39). Peripheral airways show (4) increased
intraluminal mucus and exudate, even of different composition with respect
to the one observed in COPD (5) increased mass of smooth muscle, (6) air-
way wall fibrosis, distortion, and obliteration (7) loss of alveolar attach-
ments to the bronchiolar walls. These latter pathological abnormalities,
however, have been described in the lungs of subjects who died of asthma,
and it remains unknown whether they are present in the peripheral airways
of living asthmatics.
The pathology of severe asthma is less clear. Some studies have shown
that the airway pathology of severe asthma is similar to the airway pathology
of mild asthma, in particular involving eosinophils (40), even if the
eosinophilic infiltrate looks more severe and more proximally distributed.
By contrast, other studies have shown that severe asthma has a different
pathology, with a predominance of neutrophils over eosinophils on BAL,
endobronchial biopsies, and transbronchial biopsies (41,42). Interestingly,
the thickness of the reticular layer of the basement membrane is no different
in subjects of different severity (26). A possible explanation for the differ-
ences in the inflammatory cells observed by some authors between severe,
steroid-dependent asthma and mild asthma is that the two forms of asthma
have different pathologies, with a prominent neutrophilia in steroid-depen-
dent asthma, and a prominent eosinophilia in mild asthma. An alternative
explanation is that neutrophilia in steroid-dependent asthma may be the
effect of steroid therapy itself, since glucocorticosteroids have been shown
to inhibit neutrophil apoptosis (43). Finally, it is possible that different
inflammatory cell profiles in the airways may have been caused by different
inflammatory stimuli, i.e. infectious stimuli in case of neutrophilia, and aller-
gic stimuli in case of eosinophilia.
C.
Smoking Asthmatics
The pathology of smoking asthmatics, late-onset asthmatics, nonsmoking
subjects with COPD, or subjects with COPD and large reversibility to treat-
