Understanding how a CD player works doesn't make a disc's music sound better. But if it's your job to fix CD players or tell customers when to give them up, knowing how they work helps a lot. Molecular Basis of Pulmonary Disease: Insights From Rare Lung Disorders is not an easy read, and it's not for every pulmonary physician or student of lung disease. It is a 2010 compendium of 19 chapters about 17 different rare lung diseases. Some are quite rare (eg, pulmonary capillary hemangiomatosis), but some are seen with some frequency by consulting pulmonary physicians (eg, pulmonary Langerhans cell histiocytosis), and some are relatively common (sarcoidosis).
This book's greatest appeal to me was the chapters on diseases one sees in clinical practice or presented at a conference. For several of them the book gives useful and sometimes intriguing information that provides the gratifying sensation that one is thoroughly and articulately updated about what the patient and caregivers need to know. An example is Vassallo's chapter about pulmonary Langerhans cell histiocytosis. This and other chapters dutifully adopt the latest nomenclature to keep one current in “lung-disease speak” (eg, “eosinophilic granuloma of the lung” and “histiocytosis X” are apparently passé nomenclature), but this chapter's 20 pages on this still puzzling disease update the reader about what really matters. Is the disease related to proliferative histiocytic disorders that may be prescribed chemotherapy? Yes and no: the same cell lineage is involved, but pulmonary Langerhans cell histiocytosis is nearly always polyclonal; it appears to be a reactive disorder.
In olden days, bronchoalveolar lavage fluid was collected in electron-microscopy medium for fixation and examination for cells with Birbeck granules—those intracellular tennis-racket-mimicking organelles. Then, briefly, it was CD1a antigen staining for diagnosis. And now S-100 staining is most commonly used. Are these 3 techniques similarly informative? No, they aren't: S-100 is found on many types of cells, and 5% positivity for CD1a in cells in bronchoalveolar lavage fluid, together with a consistent clinical picture, is the most secure and convenient way to make the diagnosis when electron microscopy and electron-microscopy media are not available.
Does pulmonary Langerhans cell histiocytosis occur only in cigarette smokers? No, but young adults who smoke make up over 90% of the cases in existing case series. Will smoking cessation make the disease go away? No, not in everyone. Are corticosteroids worth trying? Vassallo thinks so, when the disease is progressive (a 15% decline during monitoring of the FEV1 or diffusing capacity of the lung for carbon monoxide), and he presents his sensible approach: 0.5 mg/kg/d of prednisone for 3 months, then repeat pulmonary function testing, with rapid steroid tapering to zero if no benefit is seen. Will he try corticosteroid treatment even if a smoking patient is unable to quit cigarettes? Yes he will, and so should we.
Does pulmonary Langerhans cell histiocytosis present with both restrictive and obstructive physiology on pulmonary function testing? Yes it does, perplexing test-taking fellows and the rest of us, and Vassallo explains why: although often called an interstitial lung disease, small airways are usually involved, especially early. Progressive disease leads to fibrosis and restrictive physiology, and cysts lead to air-trapping and further obstruction.
What is the molecular basis of pulmonary Langerhans cell histiocytosis? Vassallo and other experts don't know, and he doesn't spend time “hand-waving” or describing obscure animal experiments of questionable relevance. Genetic factors are probably not involved, he writes, because the disease is sporadic and doesn't run in families. Cigarette smoke is a reliable recruiter and increaser of the population of dendritic cells in the lungs of rodents and humans, but that is not enough to commonly provoke pulmonary Langerhans cell histiocytosis. Granulocyte macrophage colony stimulating factor expression is induced by cigarette smoke and is commonly abundant on airway epithelial cells in early pulmonary Langerhans cell histiocytosis lesions, but not elsewhere in lung biopsies of uninvolved tissue in the same patient—but this may be an epiphenomenon.
Another fascinating chapter describes new information about lymphangioleiomyomatosis, which occurs clinically as a sporadic disease in which histologically benign-appearing smooth-muscle cells infiltrate all structures throughout the lungs and result in cystic changes and disabling pleural effusions. There is no explanation at present for the cystic changes. Since symptomatic lymphangioleiomyomatosis occurs solely in women during the third to fifth decade of life, empirical antagonism of estrogen action with progestins is the usual therapy tried. Its success is unproven. Perhaps this is not surprising, since lymphangioleiomyomatosis usually worsens during pregnancy, a progestational hormonal state.
In their chapter, Henske and McCormack describe the new but incomplete understanding that lymphangioleiomyomatosis is related to tuberous sclerosis, an autosomal dominantly inherited disease of benign tumors in multiple organs. Thirty to forty percent of tuberous sclerosis patients have identifiable (but usually asymptomatic and rarely progressive) areas of lymphangioleiomyomatosis in their lungs. While tuberous sclerosis complex occurs in men and women, lymphangioleiomyomatosis is found solely in women. Moreover, the current conventional wisdom is that pulmonary lymphangioleiomyomatosis represents metastasis of histologically benign smooth-muscle cells to the lung—but only in women. Why? There are 2 theories: the particular smooth-muscle cell that participates is found solely in women (this seems unlikely); or (the more favored explanation) the hormonal milieu of young adult women favors metastasis through the thoracic duct. Lymphangioleiomyomatosis cells migrate up the thoracic duct into the internal jugular vein and are distributed throughout both lungs by the pulmonary arteries.
As for other links of lymphangioleiomyomatosis to tuberous sclerosis: 80% of tuberous sclerosis cases result from a de novo mutation in one of 2 genes, leading (most often) to angiolipomas in both kidneys, and possibly to large benign tumors (“tubers”) in the brain and angiofibromas on the face. Angiolipomas's cell of origin is a somewhat immature smooth-muscle cell indistinguishable from those found in the lungs of affected lymphangioleiomyomatosis patients. The most exciting news about lymphangioleiomyomatosis is that, as in tuberous sclerosis complex, the mammalian target of rapamycin (mTOR) is over-expressed. In tuberous sclerosis this is due to a mutation in TSC1 or TSC2. Failure of inhibition of mTOR results in exuberant protein synthesis and cell proliferation in numerous cell types. Rapamycin (sirolimus), a potent immunosuppressive drug used after organ transplant, has now been tested in clinical trials in lymphangioleiomyomatosis patients and the results were promising, but without the stunning success of, for example, Gleevec in chronic myelogenous leukemia.
Some of the other chapters were less appealing to me. However, a great strength of this collection is that the writing is by experts and quite good: what is known is there in black-and-white text, diagrams, tables, color photomicrographs, reproduced computed tomography slices, and plain radiographs. This stands in contrast to reviews one finds too often these days, in which a junior author presents what resembles a book report with a senior author's name attached.
Most of this book's chapters are around 20 pages and include what you'd expect: disease epidemiology; available evidence on mechanism, including human and animal studies; clinical information on presentation, diagnosis, management, and prognosis; and abundant references. From Hermansky-Pudlak syndrome to cystic fibrosis, this compendium summarizes nearly all the uncommon lung diseases. For interested readers who prefer that approach to searching PubMed for a recent review (possibly of iffy quality), this would be a good book to have. However, since so much information about disease mechanism is a “work in progress,” and where little is known, this book's authors resort to describing complex animal experiments that may be of dubious relevance in the long term, this book may not be a good choice for everyone in the field. Moreover, it does not pretend to be a clinically useful guide.
Footnotes
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The author has disclosed no conflicts of interest.
- Copyright © 2011 by Daedalus Enterprises Inc.