Ulcerative colitis outpatient management: development and evaluation of tools to support primary care practitioners.

BACKGROUND: Current models of care for ulcerative colitis (UC) across healthcare systems are inconsistent with a paucity of existing guidelines or supportive tools for outpatient management. AIMS: This study aimed to produce and evaluate evidence-based outpatient management tools for UC to guide primary care practitioners and patients in clinical decision-making. METHODS: Three tools were developed after identifying current gaps in the provision of healthcare services for patients with UC at a Clinical Insights Meeting in 2013. Draft designs were further refined through consultation and consolidation of feedback by the steering committee. Final drafts were developed following feasibility testing in three key stakeholder groups (gastroenterologists, general practitioners and patients) by questionnaire. The tools were officially launched into mainstream use in Australia in 2014. RESULTS: Three quarters of all respondents liked the layout and content of each tool. Minimal safety concerns were aired and those, along with pieces of information that were felt to be omitted, that were reviewed by the steering committee and incorporated into the final documents. The majority (over 80%) of respondents felt that the tools would be useful and would improve outpatient management of UC. CONCLUSION: Evidence-based outpatient clinical management tools for UC can be developed. The concept and end-product have been well received by all stakeholder groups. These tools should support non-specialist clinicians to optimise UC management and empower patients by facilitating them to safely self-manage and identify when medical support is needed.

Dose tailoring of anti-tumour necrosis factor-alpha therapy delivers useful clinical efficacy in Crohn disease patients experiencing loss of response.

BACKGROUND: 'Dose tailoring' of anti-tumour necrosis factor alpha (TNF-α) therapy in Crohn disease (CD), by dose escalation, or shortening of dosing intervals, has been suggested to regain clinical response following a flare in a proportion of patients. However, reported outcome data are sparse and none exists from Australia. METHOD: In an observational multicentre, retrospective study, the impact of anti-TNF-α dose tailoring on corticosteroid use, the need for surgery and physician perception of clinical efficacy was examined in a real-world setting at six Australian adult teaching hospitals. Demographics, disease characteristics, medications, indication for and duration of dose tailoring were documented. RESULTS: Fifty-five CD patients were identified as requiring dose tailoring and secondary loss of response was the indication in 96%. Either adalimumab (64%) or infliximab (36%) was dose escalated for a median of 5 months (range 1-47), with a median of 20 months follow up (range 3-65). At 3 months, dose tailoring reduced the mean number of days on high-dose corticosteroids (45 vs 23, P = 0.01). Most (78%) patients remained resection free, and 73% of physicians reported good clinical efficacy of dose tailoring. Of those who de-escalated therapy due to induction of remission, long-term (>12 months) follow up and complete data on steroid use were available in 15/28, with 12/15 (80%) remaining steroid free at 1 year. CONCLUSION: Short-term dose tailoring regains disease response in the majority of patients with CD. Of these, most will remain free of corticosteroids at 1 year after de-escalating therapy.

A validated bowel-preparation tolerability questionnaire and assessment of three commonly used bowel-cleansing agents.

BACKGROUND AND STUDY AIMS: Bowel-cleansing studies are frequently underpowered, poorly designed, and with subjective assessments. Consensus on tolerability of the bowel-cleansing agents is thus lacking. This study developed and validated a bowel-preparation tolerability questionnaire and used it to assess the tolerability of three bowel-cleansing agents, sodium phosphate (NaP), polyethylene glycol (PEG), and sodium picosulphate (Pico), in a prospective randomized single-blinded trial of ambulatory patients. PATIENTS AND METHODS: The bowel-preparation tolerability questionnaire was validated in 125 consecutive patients and then bowel-preparation agent tolerability was assessed in 634 patients in a prospective randomized single-blinded trial. RESULTS: The questionnaire's internal consistency was satisfactory with good to excellent "test-retest" reliability for aggregate tolerability and visual analogue scores. Validity assessment confirmed it as reliable and accurate. Of 634 patients, 97.8 % took >75 % of the allocated preparation and 98.9 % completed the questionnaire. Overall, Pico was better tolerated than PEG (p < 0.001) and NaP (p < 0.001). NaP was better tolerated than PEG (p < 0.001). Regardless of the bowel-preparation agent used, males tolerated them better than females (p = 0.009) as did patients having their procedure in the AM. Older patients, however, tolerated all preparations better than younger patients (p = 0.006). CONCLUSIONS: This study used the first validated bowel-preparation tolerability questionnaire and identified that age, sex, and procedure time all impacted tolerability. Overall, Pico was best tolerated, but PEG's tolerability in patients ≥60 years was equal to that of Pico and NaP, suggesting that PEG can be recommended for older patients to avoid the electrolyte disturbances associated with the osmotic preparations.

Prevention of cancer in IBD - a balancing act.

Inflammation and immunosuppression are two major risk factors for the development of carcinogenesis in inflammatory bowel disease (IBD). While the natural history of uncontrolled inflammation in the bowel may lead to a higher incidence of colorectal cancer (CRC), surveillance colonoscopy has resulted in earlier detection of dysplasia and cancer, prompting earlier surgical intervention and improved prognosis, while chemoprevention in the form of the anti-inflammatory 5-aminosalicylate acids and immunosuppression could potentially decrease the incidence of CRC. Numerous extra-intestinal cancers such as hepatobiliary and pancreatic malignancies, however, are also noted to be more prevalent in IBD patients particularly with co-existing primary sclerosing cholangitis. Somewhat ironically, however, the medications used to control the inflammation in IBD may also be responsible for the development of other cancers. The increased risk of lymphoma and skin cancers associated with immunosuppressive medication use may potentially be due to loss of immunosurveillance and in the case of lymphoma, the presence of oncogenic viruses (i.e., Epstein-Barr virus). Thus the challenge for both the treating physician and IBD patient is to balance the risk of any potential treatment against patient symptoms and the natural history of uncontrolled inflammation from their disease.

Bowel cleansing for colonoscopy: prospective randomized assessment of efficacy and of induced mucosal abnormality with three preparation agents.

BACKGROUND AND STUDY AIMS: Bowel-cleansing studies are frequently underpowered, poorly designed, and use subjective bowel cleansing assessments. Consensus on efficacy, tolerability, and preparation-induced mucosal abnormalities is lacking. This study aimed to clarify the differences in efficacy and preparation-induced mucosal inflammation of sodium phosphate (NaP), colonLYTLEY (PEG), and Picoprep (Pico). PATIENTS AND METHODS: This was a prospective randomized single-blinded trial of ambulatory patients to assess the efficacy of bowel preparation and preparation-induced mucosal inflammation. Proceduralists who were blinded to the preparation taken, assessed both bowel cleansing by using the Ottawa bowel preparation assessment tool and preparation-induced mucosal inflammation. RESULTS: Of the 634 patients, 98 % ingested more than 75 % of the bowel preparation and data were complete for colonic preparation scoring in 99 %. The preparation used, time of procedure, and patient sex all independently impacted on bowel cleansing. NaP was less efficacious than PEG ( P < 0.001) and Pico ( P < 0.001) for morning procedures whereas all bowel preparations were equally efficacious for afternoon procedures. Preparation-induced mucosal inflammation was 10-fold greater with NaP ( P = 0.03) and Pico ( P = 0.03) compared with PEG. CONCLUSIONS: This is the largest published prospective randomized blinded study on this topic and the first to evaluate the three major classes of preparation with a validated tool. The bowel preparation used, time of procedure, and patient sex all independently impacted on bowel cleansing. NaP gave the worst preparation for morning procedures whereas all preparations were equally effective for afternoon procedures. NaP and Pico induced mucosal inflammation 10-fold more frequently than PEG, a finding that requires further investigation.

Infliximab vs. adalimumab in Crohn's disease: results from 327 patients in an Australian and New Zealand observational cohort study.

BACKGROUND: Maintenance anti-tumour necrosis factor-α (anti-TNFα) treatment for Crohn's disease is the standard of care for patients with an inadequate response to corticosteroids and immunomodulators. AIM: To compare the efficacy and safety of infliximab and adalimumab in clinical practice and assess the value of concomitant immunomodulator therapy. METHODS: We performed an observational cohort study in consecutive patients with Crohn's disease qualifying for anti-TNFα treatment in Australia and New Zealand between 2007 and 2011. Demographic and clinical data were prospectively recorded to identify independent factors associated with induction and maintenance of response to infliximab or adalimumab, or to either anti-TNFα therapy. RESULTS: Three hundred and twenty-seven patients (183 infliximab, 144 adalimumab) successfully applied for treatment. Eighty-nine percent responded in all groups and median maintenance of response was similar for the two agents. Concomitant immunomodulator with infliximab, but not adalimumab, demonstrated a significantly longer response overall (P = 0.002), and significantly fewer disease and treatment-related complications (P = 0.017). Corticosteroids at baseline, and/or in the preceding 12 months, were associated with a 9-13 times greater risk of disease flare during maintenance treatment as compared to no corticosteroids (P < 0.0001). Maintenance of response was similar in the anti-TNF naïve and anti-TNF experienced subgroups. CONCLUSIONS: In this large, real-life study, we demonstrate infliximab and adalimumab to have similar response characteristics. However, infliximab requires concomitant immunomodulator to achieve optimal maintenance of response comparable to adalimumab monotherapy. The results of this study will assist clinicians in further optimising patient care in their day-to-day clinical practice.

Review article: acute severe ulcerative colitis - evidence-based consensus statements.

BACKGROUND: Acute severe ulcerative colitis (ASUC) is a potentially life-threatening complication of ulcerative colitis. AIM: To develop consensus statements based on a systematic review of the literature of the management of ASUC to improve patient outcome. METHODS: Following a literature review, the Delphi method was used to develop the consensus statements. A steering committee, based in Australia, generated the statements of interest. Three rounds of anonymous voting were carried out to achieve the final results. Acceptance of statements was pre-determined by ≥80% votes in 'complete agreement' or 'agreement with minor reservation'. RESULTS: Key recommendations include that patients with ASUC should be: hospitalised, undergo unprepared flexible sigmoidoscopy to assess severity and to exclude cytomegalovirus colitis, and be provided with venous thromboembolism prophylaxis and intravenous hydrocortisone 100 mg three or four times daily with close monitoring by a multidisciplinary team. Rescue therapy such as infliximab or ciclosporin should be started if insufficient response by day 3, and colectomy considered if no response to 7 days of rescue therapy or earlier if deterioration. With such an approach, it is expected that colectomy rate during admission will be below 30% and mortality less than 1% in specialist centres. CONCLUSION: These evidenced-based consensus statements on acute severe ulcerative colitis, developed by a multidisciplinary group, provide up-to-date best practice recommendations that improve and harmonise management as well as provide auditable quality assessments.

Randomised clinical trial: vercirnon, an oral CCR9 antagonist, vs. placebo as induction therapy in active Crohn's disease.

BACKGROUND: Many patients with active Crohn's disease do not adequately respond to therapies, highlighting the need for new treatments. AIMS: To conduct a randomised, double-blind, placebo-controlled phase 3 study to assess the efficacy and safety of vercirnon, an oral inhibitor of CC chemokine receptor-9, for the treatment of patients with moderately-to-severely active Crohn's disease. METHODS: Patients with a Crohn's Disease Activity Index (CDAI) of 220-450, plus evidence of active disease (endoscopically confirmed or elevation of both C-reactive protein and faecal calprotectin), who had failed corticosteroid or immunosuppressant therapy were enrolled. Patients were equally randomised to receive placebo, vercirnon 500 mg once daily or vercirnon 500 mg twice daily. The primary endpoint was clinical response, defined as a 100-point decrease in CDAI from baseline to week 12. RESULTS: Six hundred and eight patients were randomised. Patient characteristics and baseline demographics were similar among the groups. The proportions of patients achieving a clinical response were 25.1%, 27.6% and 27.2% for placebo, once daily and twice daily respectively; treatment differences were not significant (2.5%; 95% confidence interval, CI -6.1% to 11.0%, P = 0.546 for once daily vs. placebo, and 2.1%; 95% CI -6.5% to 10.7%, P = 0.648 for twice daily vs. placebo). Adverse events were reported in 69.8%, 73.3% and 78.1% with serious adverse events in 8.9%, 5.9%, and 6.0% of patients in the placebo, once-daily and twice-daily groups, respectively. CONCLUSIONS: We did not demonstrate efficacy of vercirnon as an induction therapy in patients with moderately-to-severely active Crohn's disease; its effect in maintenance therapy was not addressed.

Efficacy of thiopurines and adalimumab in preventing Crohn's disease recurrence in high-risk patients - a POCER study analysis.

BACKGROUND: Crohn's disease recurs in the majority of patients after intestinal resection. AIM: To compare the relative efficacy of thiopurines and anti-TNF therapy in patients at high risk of disease recurrence. METHODS: As part of a larger study comparing post-operative management strategies, patients at high risk of recurrence (smoker, perforating disease, ≥2nd operation) were treated after resection of all macroscopic disease with 3 months metronidazole together with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine-intolerant patients received adalimumab induction then 40 mg fortnightly. Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed blind to treatment. RESULTS: A total of 101 patients [50% male; median (IQR) age 36 (25-46) years] were included. There were no differences in disease history between thiopurine- and adalimumab-treated patients. Fifteen patients withdrew prior to 6 months, five due to symptom recurrence (of whom four were colonoscoped). Endoscopic recurrence (Rutgeerts score i2-i4) occurred in 33 of 73 (45%) thiopurine vs. 6 of 28 (21%) adalimumab-treated patients [intention-to-treat (ITT); P = 0.028] or 24 of 62 (39%) vs. 3 of 24 (13%) respectively [per-protocol analysis (PPA); P = 0.020]. Complete mucosal endoscopic normality (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in 27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4) occurred in 8% vs. 4% (thiopurine vs. adalimumab). CONCLUSIONS: In Crohn's disease patients at high risk of post-operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.

Inflammation location, but not type, determines the increase in TGF-beta1 and IGF-1 expression and collagen deposition in IBD intestine.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is frequently complicated by extracellular matrix (ECM) changes that may result in fibrosis. Transforming growth factor (TGF)-beta1 and insulin-like growth factor (IGF)-1 mediate numerous ECM changes. Our aim was to determine whether TGF-beta1 and IGF-1 are involved in intestinal ECM collagen regulation and what impact the inflammatory infiltrate has on their expression. METHODS: TGF-beta1 and IGF-1 mRNA and protein were assessed in fibrosed Crohn's disease (CD), inflamed CD, inflamed ulcerative colitis (UC), and control intestine using in situ hybridization and immunohistochemistry. Collagen types I and III were quantified by electron immunohistochemistry. RESULTS: In CD, increased TGF-beta1 and IGF-1 mRNA expression was transmural. In UC, the increase was confined to the lamina propria and submucosa. In both, distribution of TGF-beta1 and IGF-1 protein matched mRNA expression and coincided with the distribution of the inflammatory infiltrate. An increase in the collagen type III:I ratio in both CD and UC also coincided with the inflammatory infiltrate. CONCLUSIONS: These findings suggest that TGF-beta1 and IGF-1 are involved in intestinal ECM remodeling in IBD, and their enhanced expression depends on the presence and location of inflammatory infiltrates rather than the type of IBD.

Altered response of intestinal mucosal fibroblasts to profibrogenic cytokines in inflammatory bowel disease.

BACKGROUND AND AIMS: Fibrosis is a major complication of inflammatory bowel disease (IBD), which may be mediated by the intestinal fibroblast. Our aim was to isolate and characterize mucosal fibroblasts from histologically normal intestine (control), ulcerative colitis (UC), inflamed Crohn's disease (CD), and fibrosed CD intestine. METHODS: Fibroblasts were characterized by light and electron microscopy and immunohistochemistry. Fibroblast collagen secretion and proliferation were determined by 3H-proline and 3H-thymidine incorporation, and the effects of exposure to interleukin (IL)-1beta, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta1, insulin-like growth factor (IGF)-1, and macrophage colony stimulating factor (M-CSF) were determined. RESULTS: No difference in doubling time was observed between the fibroblast populations from UC and CD intestine. All proliferated faster than fibroblasts from control intestine. Collagen secretion from IBD fibroblasts, independent of type, was increased compared with control fibroblasts and PDGF, bFGF, and TGF-beta1-induced collagen secretion from IBD fibroblasts. CONCLUSIONS: These results suggest the presence of an activated subpopulation of fibroblasts in both UC and CD tissue irrespective of the presence of tissue fibrosis or disease type.

Detection of liver injury in IBD using transient elastography.

BACKGROUND: Up to 5% of inflammatory bowel disease (IBD) patients are thought to have clinically significant liver disease due to multifactorial causes, however, this figure may be an underestimate due to reliance on abnormal liver tests (LTs) and/or liver biopsies. AIMS: Our aim was to evaluate the prevalence of clinically significant liver disease in IBD patients as defined by an increased liver stiffness measurement (LS) ≥8kPa using transient elastography (TE). METHODS: 110 IBD patients, and 55 non-IBD control subjects, had their LS recorded using FibroScan® (EchoSense, Paris, France) by a single blinded operator trained in TE. RESULTS: 71 Crohn's disease and 39 ulcerative colitis subjects were included. All demographic variables were similar between the IBD and control groups apart from a significantly higher proportion of IBD patients who smoked (17.3% vs 3.6%, P=0.013). Seven IBD patients (6.4%) had an LS over 8 kPa and 3 had persistently elevated LS 6 months later. One patient had compensated cirrhosis. No significant differences in overall LS were observed between the IBD and control groups. Increased BMI and age, however, were independently associated with a higher LS in the IBD but not in the control group (P<0.001 and 0.010 respectively). CONCLUSION: Using TE, the prevalence of clinically significant liver disease in IBD patients is low. The association of increased BMI and age with increased LS in IBD suggests fatty liver disease being the prevailing aetiology in these patients.

Implementing guidelines on the prevention of opportunistic infections in inflammatory bowel disease.

INTRODUCTION: Opportunistic infections are a key safety concern in the management of patients with inflammatory bowel disease (IBD). Despite the existence of international guidelines, many gastroenterologists have not adopted routine screening and vaccination. The aim of this study was to modify clinical behaviour by use of a simple screening tool. METHODS: A screening and vaccination proforma for hepatitis B, varicella, Influenza, Pneumococcus, human papillomavirus, tuberculosis, hepatitis C and HIV was provided to each participating gastroenterologist. Gastroenterologists were surveyed for awareness of vaccine recommendations and current practice prior to and following the introduction of the proforma. Rates of immunity and the proportion of patients receiving the recommended screening and vaccinations were documented. RESULTS: 30 gastroenterologists at 8 different IBD centres took part in the assessment. A total of 919 patients were included (55% female, 65% Crohn's, 33% ulcerative colitis, 2% indeterminate IBD). Introduction of the proforma increased self-reported gastroenterologist screening from 47% to 97% pre- and post-intervention respectively, p<0.001. After the proforma was applied, vaccination against hepatitis B, varicella, Influenza, and Pneumococcus was recommended in 67%, 2.5%, 75% and 69% of the patients respectively. Of these, 42%, 39%, 66% and 49% patients followed the recommendations and were vaccinated. Cervical smears were recommended in 31%, with 62% of these obtaining the recommended cervical smear. CONCLUSIONS: Implementation of a screening and vaccination proforma significantly changed gastroenterologist self-reported behaviour. Patient compliance with these recommendations was not optimal and suggests the need for further patient education, in addition to other forms of support.

Understanding the use of immunosuppressive agents in the clinical management of IBD.

The advent of the biological era has seen many improvements in the management of inflammatory bowel disease (IBD). These agents, however, are not a ubiquitous panacea as they are neither universally available nor are they universally efficacious in the short or long-term. There is, therefore, still a need for other therapies and it is important to remember about the medications that have been effective in the past. The use of azathioprine and 6-mercoptopurine has been the mainstay of long-term therapy for many IBD patients for many years. Their role as steroid sparing agents and in the maintenance of remission is well recognized, and with the advent of metabolite testing their use has been refined. Methotrexate is a second line immunomodulator with less impressive data but still with observed benefits in Crohn's disease (CD) and two newer immunosuppressive agents, mycophenylate mofetil and tacrolimus have sparked some interest as they appear to be efficacious in some patients. As IBD is a chronic incurable condition that primarily presents in young patients, the treating clinician's goal is to induce and maintain long-term remission. So when one agent is ineffective, or unavailable, other agents need to be considered. This review aims to provide clinicians with practical and up to date knowledge about the use of the immunomodulators in the management of IBD, which is vital in order to offer the best management for their patients.

Randomised clinical trial: certolizumab pegol for fistulas in Crohn's disease - subgroup results from a placebo-controlled study.

BACKGROUND: Treatment options for fistulizing Crohn's disease (CD) are limited. AIM: To examine whether fistula closure is maintained at week 26 following treatment with certolizumab pegol. METHODS: Patients with draining fistulas at baseline from PRECiSE 2 (n = 108) received open-label induction with certolizumab pegol 400 mg at weeks 0 (baseline), 2 and 4. Response was defined as ≥100-point decrease from baseline in the Crohn's Disease Activity Index. Nonresponders (50/108) were excluded. At week 6, responders with draining fistulas (N = 58) were randomised to certolizumab pegol 400 mg (n = 28) or placebo (n = 30) every 4 weeks across weeks 8-24. Fistula closure was evaluated throughout the study, with a final assessment at week 26. RESULTS: The majority of patients (55/58) had perianal fistula. At week 26, 36% of patients in the certolizumab pegol group had 100% fistula closure compared with 17% of patients receiving placebo (P = 0.038). Protocol-defined fistula closure (≥50% closure at two consecutive post-baseline visits ≥3 weeks apart) was not statistically significant (P = 0.069) with 54% and 43% of patients treated with certolizumab pegol and placebo achieving this end point, respectively. CONCLUSION: Continuous treatment with certolizumab pegol improves the likelihood of sustained perianal fistula closure compared with placebo.

Rectal tacrolimus in the treatment of resistant ulcerative proctitis.

BACKGROUND: Resistant ulcerative proctitis can be extremely difficult to manage. Oral tacrolimus can be effective, but may have numerous adverse effects. Topically administered tacrolimus, however, may also be effective in proctitis. Aim To undertake a pilot study to assess a potential role for topical tacrolimus in the management of resistant ulcerative proctitis. METHODS: Patients with resistant ulcerative proctitis were assessed prospectively by the colitis activity index (CAI) and Modified Mayo score. Topical rectal tacrolimus ointment was commenced at 0.3 mg/mL 3 mL b.d. and increased depending on clinical response. CAI and modified Mayo scores were assessed at 0 and 8 weeks, as were steroid usage and adverse effects. RESULTS: Eight patients (five male/three female) with inflammation to a maximum of 30 cm from the anus were included. All patients had failed disease control with 5-aminosalicylic acids, steroids, immunosuppressants and infliximab therapy. The mean initial CAI was 12.1 (range 9-16) and the mean modified Mayo score was 8.0 (range 6-9). After 8 weeks, six of eight patients achieved remission with steroids reduced or ceased in five of six. There were no significant adverse effects. CONCLUSIONS: This prospective pilot study demonstrated that topical rectal tacrolimus ointment can be effective in ulcerative proctitis. The preparation was well tolerated with no significant adverse effects. Further controlled studies are required.

Ulcerative colitis and Crohn's disease: distinctive gene expression profiles and novel susceptibility candidate genes.

To elucidate the biological dysregulation underlying two forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), we examined global gene expression profiles of inflamed colonic tissue using DNA microarrays. Our results identified several genes with altered expression not previously linked to IBD. In addition to the expected upregulation of various cytokine and chemokine genes, novel immune function-related genes such as IGHG3, IGLL2 and CD74, inflammation-related lipocalins HNL and NGAL, and proliferation-related GRO genes were over-expressed in UC. Certain cancer-related genes such as DD96, DRAL and MXI1 were differentially expressed only in UC. Other genes over-expressed in both UC and CD included the REG gene family and the calcium-binding S100 protein genes S100A9 and S100P. The natural antimicrobial defensin DEFA5 and DEFA6 genes were particularly over-expressed in CD. Overall, significant differences in the expression profiles of 170 genes identified UC and CD as distinct molecular entities. The genomic map locations of the dysregulated genes may identify novel candidates for UC and CD genetic susceptibility.

A study of respiratory infections in a healthy adult population during the 1987 Australian winter.

During the 1987 Australian winter, respiratory illness patterns were studied in a population of 454 healthy adults, aged 18-59, over a period of 45 days. These patterns were matched with data obtained from laboratory diagnoses for respiratory viruses, Mycoplasma pneumoniae and bacteria. Influenza B/1/86 was by far the most prevalent pathogen but other viruses including influenza A, paramyxoviruses, respiratory syncytial virus and coronavirus OC-43 were also present, either alone or in combination during the sampling period. Overall, 92 males and 101 females experienced one episode, 12 males and 22 females experienced two episodes and four females experienced three episodes. However, there were only 52 instances of viral or M. pneumoniae infections, of which 37 had a defined aetiology, while the remainder were clinically silent. No bacterial pathogens could be detected from throat swabs taken from 15 of 37 volunteers in whom a viral infection was detected, or from 43 of 70 volunteers who did not experience such infections. The study indicates that major deficiencies in our understanding of the aetiology of respiratory viral illness are probably due to methodological problems in obtaining laboratory diagnoses for many respiratory viruses, and that great difficulties exist in establishing an aetiology for respiratory infections based upon clinical symptoms alone.