Lyrics · 完整歌詞
Occupational lung disease illustrates how a brief encounter with an inhaled particle
can initiate a biological response that persists for decades.
When an asbestos fibre, fine enough to reach the lower lobes,
is engulfed by an alveolar macrophage,
the cell can neither digest nor release it;
instead it coats the fibre in iron-rich protein,
producing the beaded asbestos body.
The trapped fibre keeps releasing reactive oxygen species and inflammatory cytokines,
and over decades this smouldering injury is written into three different lesions:
calcified pleural plaques, diffuse interstitial fibrosis and malignant mesothelioma.
Asbestos bodies lie most readily in the seemingly normal parenchyma beside a
tumour rather than within it;
they prove exposure, never diagnosis, and mesothelioma is confirmed by thoracoscopic biopsy.
Asbestos favours the lower zones and the pleura,
and its malignant companions are mesothelioma and bronchogenic carcinoma,
the latter multiplied by cigarette smoke,
whereas pulmonary lymphoma is not an asbestos disease.
Silica, by contrast,
settles in the upper lobes with eggshell calcification
and a raised risk of tuberculosis,
while plaques are inert scars that never transform.
Occupational lung disease illustrates how a brief encounter with an inhaled particle
can initiate a biological response that persists for decades.
A peripheral nodule invites a second line of reasoning,
this time about the cell of origin.
Tumours arising from small airways sit at the periphery
and are usually adenocarcinomas,
the histology of never-smokers and of the EGFR
and ALK alterations that respond to oral tyrosine-kinase inhibitors.
Tumours arising from the central bronchi are either squamous, with keratin pearls,
cavitation and parathyroid hormone-related peptide that raises calcium without bone metastases,
or small cell carcinomas of neuroendocrine lineage, which declare themselves through SIADH,
ectopic ACTH or Lambert-Eaton syndrome,
and are treated with chemotherapy rather than surgery.
Mechanism likewise separates the two causes of trapped air.
Emphysema is an imbalance of proteases and their inhibitors:
neutrophils and macrophages recruited by smoke release elastase and matrix metalloproteinase-12,
alpha-1 antitrypsin is overwhelmed or,
in the young non-smoker with lower-lobe panacinar disease, congenitally deficient,
and elastic fibres are digested until the acinus dilates
and recoil is lost.
Asthma travels the opposite road:
smooth muscle that contracts daily against histamine
and leukotrienes is trained rather than tired,
and consequently it hypertrophies.
Spirometry asks three questions in sequence.
Is expiration too slow?
A post-bronchodilator FEV1 to FVC ratio below 0.70 establishes obstruction.
Is the lung too small?
Restriction is confirmed only by a total lung capacity below 80 per cent of
predicted,
because a reduced FVC may merely reflect gas trapped behind narrowed airways.
Is gas exchange impaired?
A reduced diffusing capacity localises the injury to the alveolar wall,
so that obstruction with a low DLCO suggests emphysema
whereas a preserved DLCO suggests asthma,
and restriction with a low DLCO suggests fibrosis
whereas a normal DLCO with weak inspiratory pressures points to neuromuscular disease.
Reversibility demands both a rise of at least 12 per cent
and at least 200 millilitres;
one criterion without the other proves nothing,
and even a positive test cannot exclude COPD.
Occupational lung disease illustrates how a brief encounter with an inhaled particle
can initiate a biological response that persists for decades.