Effects of second hand smoke on airway secretion and mucociliary clearance.
Key-event relationships
Goblet cell hyperplasia leads to impaired mucociliary clearance
The review's central claim: active and passive cigarette smoke exposure produces hyperplasia of goblet cells and submucosal glands, which raises the secretory capacity of the airway and thereby impairs mucociliary clearance. Stated for COPD arising from both active smoking and second-hand smoke.
Active and passive CS-induced chronic obstructive pulmonary disease (COPD) is frequently associated with hyperplasia of goblet cells and submucosal glands (SMGs), thus increasing the secretory capacity of the airways that impairs MCC.
The review states the hyperplasia-to-impaired-MCC link directly, and attributes it to both active and passive (second-hand) smoke.
Goblet cell hyperplasia leads to mucin hypersecretion
Goblet cell metaplasia and hyperplasia is described as the major airway remodeling change in COPD, and the review states that it results in airway mucus hypersecretion.
One major characteristics of airway remodeling in COPD is airway goblet cells metaplasia and hyperplasia, which results in airway mucus hypersecretion.
The review names goblet cell metaplasia/hyperplasia as the cause of airway mucus hypersecretion in COPD.
EGFR activation leads to mucin hypersecretion
The first of several mechanisms the review lists for smoke-induced mucus hypersecretion: cigarette smoke drives mucin production through epidermal growth factor receptor activation, reported both in vitro and in vivo. The review also notes a TACE-proligand-EGFR route to mucin overproduction.
CS could cause mucin production via epidermal growth factor receptor (EGFR) activation both in vitro and in vivo
The review lists EGFR activation first among the mechanisms responsible for cigarette-smoke-induced mucus hypersecretion.
Airway inflammation leads to mucin hypersecretion
The review's neutrophil-dependent route to mucus hypersecretion: smoke promotes goblet cell metaplasia indirectly through activation and recruitment of neutrophils and subsequent epithelial cell oxidative stress, and neutrophil products themselves drive mucin release from surface epithelial cells.
In vivo, neutrophils and neutrophil products can cause the upregulation and release of mucin from surface epithelial cells
The review states that neutrophils and their products upregulate and release mucin from airway surface epithelial cells.
Goblet cell hyperplasia leads to club cell marker loss
The review states that new goblet cells are produced at the expense of progenitor cells, so serous and Clara (club) cell numbers fall as goblet cell numbers rise. It notes this matters because those cells supply anti-inflammatory, immunomodulatory and antibacterial molecules. The review reports a decrease in Clara cell NUMBER; the shared key event on main is worded as club cell marker loss.
the progenitor cells, most notably serous and Clara cells, which decrease in number as goblet cell numbers increase
The review couples the rise in goblet cell number to a fall in serous and Clara (club) cell number, because goblet cells are produced at the progenitors' expense.
Altered ciliogenesis leads to decreased ciliary function
The review states outright that second-hand smoke reduces ciliated cell number, ciliogenesis, and ciliary beat frequency — so the ciliogenesis defect and the loss of ciliary function are asserted together for SHS.
SHS decreases not only ciliated cells and ciliogenesis but also CBF.
A single sentence in which the review attributes decreased ciliated cell number, decreased ciliogenesis, and decreased CBF to SHS.
Decreased ciliary beat frequency leads to impaired mucociliary clearance
The review defines MCC as requiring normal ciliary beat frequency alongside adequate periciliary liquid volume and balanced mucus, and states that inhaled SHS lowers CBF. Ciliary beats supply the physical force that moves mucus, and CBF sets the speed of that movement.
MCC is characterized by the upward movement of mucus by ciliary motion that requires a balance between the volume and composition of the mucus, adequate periciliary liquid (PCL) volume, and normal ciliary beat frequency (CBF).
The review makes normal CBF one of the three stated requirements for mucociliary clearance, so a fall in CBF impairs MCC.
Ciliary beats provide the required physical force to move mucus and the trapped foreign particles
States the mechanism by which ciliary beating drives clearance, which a reduced beat frequency degrades.
Decreased ciliary function leads to impaired mucociliary clearance
The review's conclusion couples smoke-induced impairment of cilia beating to the loss of normal MCC, and elsewhere describes CS-induced MCC dysfunction as involving adverse effects on the structure and function of cilia.
changes in airway secretion and impairment of cilia beating that are critical to a normal MCC
From the conclusions: the review names impaired cilia beating as critical to the loss of normal MCC after CS/SHS exposure.
CS-induced MCC dysfunction is complex and incompletely understood, but it involves adverse effects on the structure and function of cilia
The review places ciliary structure and function among the causes of CS-induced MCC dysfunction, while noting the mechanism is incompletely understood — the basis for evidence_support: moderate.
Decreased ASL height leads to impaired mucociliary clearance
The review lists decreased luminal liquid, alongside increased mucin production and impaired cilia beating, as a change with deleterious consequences for airway health including mucus stasis. It separately names adequate periciliary liquid volume as a requirement for MCC, with the PCL "sol" layer height approximating outstretched cilia length (about 7 micrometres).
Increased mucin production, decreased luminal liquid, and impaired cilia beating motion in COPD have deleterious consequences for airway health, including mucus stasis and airway infection.
The review names decreased luminal liquid as one of three changes that produce mucus stasis, i.e. failed clearance.
with a height that approximates the length of the outstretched cilia (about 7 μm) and keeps mucus at an optimal distance from the underlying epithelia
Gives the review's structural rationale: the periciliary liquid layer must match cilia length to hold mucus at the distance that permits clearance.
Impaired mucociliary clearance leads to airway inflammation
The review proposes that smoke-decreased MCC in COPD leads to airway infection, which in turn leads to inflammation and fibrosis, and that CS/SHS-impaired MCC raises infection rate and disease severity in a way that could be associated with COPD exacerbations. Presented by the authors as a suggestion, hence weak support.
It is suggested that a CS-decreased MCC in COPD may lead to airway infection
The review offers the MCC-to-infection step as a suggestion; the same sentence continues to inflammation and fibrosis. Quoted only as far as the review's own hedged wording goes.
CS/SHS-impaired MCC results in the increased infection rate and disease severity that could be associated with COPD exacerbations.
The conclusion restates the consequence of impaired MCC as increased infection and disease severity.
Mucin hypersecretion leads to decreased lung function
The review cites epidemiological data associating mucus hypersecretion with a more rapid decline in FEV1 and increased hospitalization among COPD patients. No effect size is given in this paper, so the quantitative understanding is low.
associated with a more rapid decline in FEV1 and increased hospitalization of patients with COPD
The review reports the epidemiological association between mucus hypersecretion and accelerated FEV1 decline, an organ-level loss of lung function.