Pulmonary-intestinal cross-talk in mucosal inflammatory disease.

Mycobacterium avium subspecies paratuberculosis (MAP) is a member of the M avium complex (MAC) It differs genetically from other MAC in having 14 to 18 copies of IS900 and a single cassette of DNA involved in the biosynthesis of surface carbohydrate Unlike other MAC, MAP is a specific cause of chronic inflammation of the intestine in many animal species, including primates The disease ranges from pluribacillary to paucimicrobial, with chronic granulomatous inflammation like leprosy in humans MAP infection can persist for years without causing clinical disease The herd prevalence of MAP infection in Western Europe and North America is reported in the range 21% to 54% These subclinically infected animals shed MAP in their milk and onto pastures MAP is more robust than tuberculosis, and the risk that is conveyed to human populations in retail milk and in domestic water supplies is high MAP is harboured in the ileocolonic mucosa of a proportion of normal people and can be detected in a high proportion of full thickness samples of inflamed Crohn's disease gut by improved culture systems and IS900 polymerase chain reaction if the correct methods are used MAP in Crohn's disease is present in a protease-resistant nonbacillary form, can evade immune recognition and probably causes an immune dysregulation As with other MAC, MAP is resistant to most standard antituberculous drugs Treatment of Crohn's disease with combinations of drugs more active against MAC such as rifabutin and clarithromycin can bring about a profound improvement and, in a few cases, apparent disease eradication New drugs as well as effective MAP vaccines for animals and humans are needed The problems caused by MAP constitute a public health issue of tragic proportions for which a range of remedial measures are urgently needed

/pdf/causation-of-crohn-s-disease-by-mycobacterium-avium-1m4r7a6myj.pdf

Causation of Crohn's disease by Mycobacterium avium subspecies paratuberculosis

https://journal.chestnet.org/article/S0012-3692(15)48340-0/pdf

Thoracic manifestations of inflammatory bowel disease.

Extraintestinal manifestations of both Crohn's disease and ulcerative colitis (UC) have been well described, although pulmonary findings are often overlooked. We summarize the experience of more than 400 cases of pulmonary manifestations of inflammatory bowel disease (IBD). These manifestations will be categorized by disease mechanism into drug-induced disease, anatomic disease, over-lap syndromes, autoimmune disease, physiologic consequences of IBD, pulmonary function test abnormalities, and nonspecific lung disease. We intend to provide the clinician with a practical working update on the spectrum of pulmonary dysfunction associated with IBD.

Pulmonary manifestations of inflammatory bowel disease

In South Wales, United Kingdom, a populated coastal region lies beneath hill pastures grazed by livestock in which Mycobacterium avium subsp. paratuberculosis is endemic. The Taff is a spate river running off the hills and through the principal city of Cardiff. We sampled Taff water above Cardiff twice weekly from November 2001 to November 2002. M. avium subsp. paratuberculosis was detected by IS900 PCR and culture. Thirty-one of 96 daily samples (32.3%) were IS900 PCR positive, and 12 grew M. avium subsp. paratuberculosis bovine strains. Amplicon sequences from colonies were identical to the sequence with GenBank accession no. X16293, whereas 16 of 19 sequences from river water DNA extracts had a single-nucleotide polymorphism at position 214. This is consistent with a different strain of M. avium subsp. paratuberculosis in the river, which is unculturable by the methods we used. Parallel studies showed that M. avium subsp. paratuberculosis remained culturable in lake water microcosms for 632 days and persisted to 841 days. Of four reservoirs controlling the catchment area of the Taff, M. avium subsp. paratuberculosis was present in surface sediments from three and in sediment cores from two, consistent with deposition over at least 50 years. Previous epidemiological research in Cardiff demonstrated a highly significant increase of Crohn's disease in 11 districts. These bordered the river except for a gap on the windward side. A topographical relief map shows that this gap is directly opposite a valley open to the prevailing southwesterly winds. This would influence the distribution of aerosols carrying M. avium subsp. paratuberculosis from the river.

/pdf/mycobacterium-avium-subsp-paratuberculosis-in-the-catchment-2ob77ih41s.pdf

Mycobacterium avium subsp. paratuberculosis in the Catchment Area and Water of the River Taff in South Wales, United Kingdom, and Its Potential Relationship to Clustering of Crohn's Disease Cases in the City of Cardiff

We have investigated the following pulmonary related parameters in 22 patients with Crohn's disease who were free of clinical pulmonary symptoms and had normal chest roentgenograms and in 25 controls: serum angiotensin converting enzyme, pulmonary function tests, bronchoalveolar lavage (lymphocyte count and subpopulations, macrophage viability and superoxide anion release by macrophages) and pulmonary scannings. Serum angiotensin converting enzyme was lower in Crohn's disease (14.1 +/- 5.1) than in controls (25.2 +/- 4.7) (p less than 0.001). Twelve of 22 Crohn's disease (54%) had a bronchoalveolar lavage lymphocytosis (greater than 18% alveolar lymphocytes). Bronchoalveolar lavage lymphocytes subpopulations were quite variable. Twelve of 17 Crohn's disease (71%) had an increase spontaneous and/or stimulated superoxide anion production by alveolar macrophages. Six of 12 Crohn's disease (50%) had an increase physiologic dead space in the upper part of their lung against one of 11 controls (9%). These data suggest that most patients with Crohn's disease have a latent pulmonary involvement.

https://gut.bmj.com/content/gutjnl/27/8/919.full.pdf

Y Riou

Papers

Latent pulmonary involvement in Crohn's disease: biological, functional, bronchoalveolar lavage and scintigraphic studies.