Biomedical Engineering Reference
In-Depth Information
Inducers of Goblet Cell Apoptosis
Hyperplastic airway goblet cells in COPD models express the antiapoptotic
factor Bcl-2 (130). Conversely, the pro-apoptotic factor Bax is crucial for
resolution of hyperplasia (131). Thus, the balance between Bcl-2 and Bax
may affect the persistence of goblet cell hyperplasia. Reduction of Bcl-2
expression by antisense oligonucleotides induces a dose-dependent resolu-
tion of hyperplasia.
Mucus Inhibition vs. Mucus Hydration
The purine nucleotides, adenosine 5'-triphosphate (ATP) and uridine tri-
phosphate (UTP), increase airway mucin and water secretion via interaction
with P
2Y2
purinoceptors (132,133). Consequently, P
2Y2
antagonists might be
effective in inhibiting airway hypersecretion (134). However, mucus hydra-
tion is associated with improvements in mucociliary clearance and stimula-
tion of water secretion may have greater therapeutic potential than
inhibition of P
2Y2
-mediated mucin secretion (6). Consequently, there is con-
siderable interest in development of P
2Y2
agonists. In phase I clinical trial, a
second generation P
2Y2
agonist, INS365, was safe, well tolerated and signif-
icantly enhanced sputum expectoration (132). However, uncontrolled thin-
ning of airway mucus may have adverse clinical effects (see the section on
Contraindications to Mucolytic Therapy).
VII. CHEST PHYSIOTHERAPY
Chest physiotherapy aims to facilitate mucus clearance and encompasses
forced expiratory manoeuvres, postural drainage, chest percussion, clap-
ping, vibration, high frequency oscillation, breathing exercises, and induc-
tion of cough (135-137). In general, these techniques have been poorly
studied in COPD and there is little evidence of clinical benefit, particularly
in exacerbations. The efficiency of airflow transport and cough are depen-
dent on three factors:
1. Airflow velocity. At high airflow velocities there is a characteristic
interaction between gas and liquid called annular flow which
increases mucus transport to a level where airflow velocity is
directly related to mucus transport (138).
2. Thickness of the mucus layer. The minimal flow velocity at which
mucus transport by gas liquid interaction arises is dependent on
the thickness of the mucus layer (139). With increasing thickness
of the mucus layer, the airflow velocity needed for cough trans-
port decreases.
3. Peak expiratory flow. The peak expiratory flow developed during
a forced expiration is important because a decreased PEF mini-
mizes the effectiveness of forced expiration. The rapid application
