C. P. Bredin

The Role of Substance P in Inflammatory Disease

The diffuse neuroendocrine system consists of specialised endocrine cells and peptidergic nerves and is present in all organs of the body. Substance P (SP) is secreted by nerves and inflammatory cells such as macrophages, eosinophils, lymphocytes, and dendritic cells and acts by binding to the neurokinin‐1 receptor (NK‐1R). SP has proinflammatory effects in immune and epithelial cells and participates in inflammatory diseases of the respiratory, gastrointestinal, and musculoskeletal systems. Many substances induce neuropeptide release from sensory nerves in the lung, including allergen, histamine, prostaglandins, and leukotrienes. Patients with asthma are hyperresponsive to SP and NK‐1R expression is increased in their bronchi. Neurogenic inflammation also participates in virus‐associated respiratory infection, non‐productive cough, allergic rhinitis, and sarcoidosis. SP regulates smooth muscle contractility, epithelial ion transport, vascular permeability, and immune function in the gastrointestinal tract. Elevated levels of SP and upregulated NK‐1R expression have been reported in the rectum and colon of patients with inflammatory bowel disease (IBD), and correlate with disease activity. Increased levels of SP are found in the synovial fluid and serum of patients with rheumatoid arthritis (RA) and NK‐1R mRNA is upregulated in RA synoviocytes. Glucocorticoids may attenuate neurogenic inflammation by decreasing NK‐1R expression in epithelial and inflammatory cells and increasing production of neutral endopeptidase (NEP), an enzyme that degrades SP. Preventing the proinflammatory effects of SP using tachykinin receptor antagonists may have therapeutic potential in inflammatory diseases such as asthma, sarcoidosis, chronic bronchitis, IBD, and RA. In this paper, we review the role that SP plays in inflammatory disease. J. Cell. Physiol. 201: 167–180, 2004.

Tuberculosis due to Mycobacterium bovis in humans in the south-west region of Ireland: is there a relationship with infection prevalence in cattle?

OBJECTIVE To compare the incidence of tuberculosis due to Mycobacterium bovis in humans to the prevalence of M. bovis infection in cattle in south-west Ireland and discuss possible links between them. SETTING In the south-west region of Ireland, a mixed urban and rural community (pop. 536,000), there is a residuum of human tuberculosis caused by M. bovis. METHODS A retrospective analysis of the incidence of culture-positive M. bovis disease in humans in south-west Ireland from 1983 to 1994 and of the results of tuberculin testing in cattle from 1978 to 1994 for the same region. RESULTS One to five cases of human tuberculosis due to M. bovis were recorded per year while the overall prevalence of bovine infection fell gradually during the period of study from 467 tuberculin-positive animals per 100,000 cattle tested in 1983 to 158 per 100,000 in 1994. CONCLUSION The low incidence plateau of human tuberculosis due to M. bovis together with the decline in prevalence of animal infection in the overall period studied suggest a cut-off in the animal to human chain of infection at two points; the animal source and the ingestion of (now pasteurized) milk. This would suggest that disease in humans is now due to reactivation of previous foci of infection which were acquired when milk pasteurization was not compulsory. Based on this, we would anticipate a further reduction and possible elimination of human tuberculosis due to M. bovis in this region in the next 10-15 years.

Upregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis.

Substance P (SP) is a proinflammatory neuropeptide that is secreted by sensory nerves and inflammatory cells. Increased levels of SP are found in sarcoid bronchoalveolar lavage fluid. SP acts by binding to the neurokinin-1 receptor and increases secretion of tumor necrosis factor-α in many cell types. We sought to determine neurokinin-1 receptor expression in patients with sarcoidosis compared with normal controls. Neurokinin-1 receptor messenger RNA and protein expression were below the limits of detection by reverse transcriptase-polymerase chain reaction and immunohistochemistry in peripheral blood mononuclear cells of healthy volunteers (n = 9) or patients with stage 1 or 2 pulmonary sarcoidosis (n = 10), but were detected in 1/9 bronchoalveolar lavage cells of controls compared with 8/10 patients with sarcoidosis (p = 0.012) and 2/9 biopsies of controls compared with 9/10 patients with sarcoidosis (p = 0.013). Immunohistochemistry localized upregulated neurokinin-1 receptor expression to bronchial and alveolar epithelial cells, macrophages, lymphocytes, and sarcoid granulomas. The patient in whom neurokinin-1 receptor was not detected was taking corticosteroids. Incubation of the type II alveolar and bronchial epithelial cell lines A549 and SK-LU 1 with dexamethasone downregulated neurokinin-1 receptor expression. Upregulated neurokinin-1 receptor expression in patients with sarcoidosis may potentiate substance P-induced proinflammatory cytokine production in patients with sarcoidosis.

Allergic bronchopulmonary aspergillosis: A rare cause of pleural effusion

Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Allergic bronchopulmonary aspergillosis (ABPA) is a syndrome seen in patients with asthma and cystic fibrosis, and is characterized by hypersensitivity to chronic colonization of the airways with A. fumigatus. We report the case of a patient with ABPA presenting with pleural effusion. A 27‐year‐old male was referred with recurrent right pleural effusion. Past medical history was remarkable for asthma, allergic sinusitis, and recurrent pleurisy. Investigations revealed peripheral eosinophilia with elevated serum immunoglobulin E and bilateral pleural effusions with bilateral upper lobe proximal bronchiectasis. Precipitating serum antibodies to A. fumigatus were positive and the A. fumigatus immediate skin test yielded a positive reaction. A diagnosis of ABPA associated with bilateral pleural effusions was made and the patient was commenced on prednisolone. At review, the patient’s symptoms had considerably improved and his pleural effusions had resolved. ABPA may present with diverse atypical syndromes, including paratracheal and hilar adenopathy, obstructive lung collapse, pneumothorax and bronchopleural fistula, and allergic sinusitis. Allergic bronchopulmonary aspergillosis is a rare cause of pleural effusion and must be considered in the differential diagnosis of patients presenting with a pleural effusion, in particular those with a history of asthma.

Farmer’s Lung in Ireland (1983–1996) remains at a constant level

A prospective study was undertaken by the Departments of Respiratory Medicine and Medical Microbiology at the Cork University Hospital, a. to investigate the epidemiology of Farmer’s Lung (F.L.) in the Republic of Ireland (pop. 3.5 million), with special reference to the South Western Region of this country (pop. 536,000) and b. to assess any relationship between the prevalence/incidence of F.L. with climatic factors in South West Ireland, between 1983 and 1996. F.L. incidence remained constant throughout the 13 yrs studied both on a national and a regional basis. A significant relationship was also found between total rainfall each summer and F.L. incidence and prevalence over the following yr (p<0.005) in South-West Ireland. The persistence of F.L. in Ireland at a constant level suggests that farmers’ working environment and farm practices need to be improved.

Isolation of Mycobacterium chelonae in a bronchoscopy unit and its subsequent eradication

SETTING Contamination events with Mycobacterium chelonae in 7 patients undergoing bronchoscopy, out of a total of 100 patients in a 5-month period, were analysed. OBJECTIVE To identify and assess the importance of factors thought to be relevant in the aetiology of these contamination events and by removing these factors, to eradicate the problem of continuing M. chelonae contamination. DESIGN A retrospective analysis of the frequency of M. chelonae isolates from bronchoalveolar fluid, assessing the contribution of the following measures to the eradication of M. chelonae: (1) changes to the bronchoscopy units water supply; (2) insertion of bacterial filters; (3) installation of a new semi-automated cleaning machine incorporating an ultrasound cycle; (4) staff training in correct use of the new equipment. RESULTS Following the discontinuation of using tapwater in the cleaning process, the above changes resulted in complete eradication of contamination events, with no further events occurring in the following 12 months. CONCLUSION Insertion of bacterial filters into the water supply, with the addition of a more sophisticated semi-automatic cleaning machine involving an ultrasound cycle in addition to conventional cleaning methods currently used, will help reduce or eradicate contamination events with M. chelonae in bronchoscopy units.

Endometrial and Pulmonary Sarcoidosis

SummaryA 33 year old woman with irregular menses due to endometrial sarcoidosis And a family history of sarcoidosis is described. Its relative increase in importance in the wake of the decline in the incidence of genital tract tuberculosis in Ireland is discussed.

Laparoscopic cholecystectomy in adult cystic fibrosis.

Two female patients with Cystic Fibrosis, attending the Adult Regional Cystic Fibrosis centre at the Cork University Hospital, were investigated for upper abdominal pain and found to have gallstones at ultrasonography. Laparoscopic cholecystectomy was performed successfully and, without complication, in both patients.

The Melkersson Rosenthal syndrome--a differential diagnosis of facial sarcoidosis.

SummaryA patient with the rare Melkersson-Rosenthal Syndrome is presented, illustrating the features of this disorder, its tendency to present to a multiplicity of specialists and drawing attention to the latest immunogenetic aspects surrounding its origin.

Airways obstruction in survivors of thoracoplasty: reversibility is greater in non-smokers.

Objective:  Before the advent of antituberculous chemotherapy, thoracoplasty (TPL) was the definitive form of therapy for cavitary pulmonary tuberculosis. This study aimed to characterize the late functional sequelae of TPL, and to establish the degree of reversibility of any consequent airway obstruction.