Jo A. Douglass

Young people with chronic illness: the approach to transition.

As increasing numbers of young people with chronic illness reach adulthood, their ongoing medical care must evolve to be delivered in an adult rather than paediatric setting, a process known as transition. Towards this goal, increasing numbers of paediatric and adult hospitals are engaging in processes to promote the continuity of care for young people with chronic illness. Increasing evidence shows that adverse health consequences occur when inadequate transition arrangements are in place. This article draws from the experience of a transition programme emanating from the Royal Children’s Hospital, Melbourne and describes the preparation that can ensure effective transition of young people with chronic illness to adult institutions. In paediatric settings, this includes opportunities for young people to be seen medically on their own to encourage independence with health‐care goals and ensuring that adequate health information is transferred to the adult service. In adult institutions, understanding the concept of adolescent development will encourage young people’s engagement with the new health‐care providers to improve health outcomes. Joint clinics between paediatric and adult health‐care teams can improve the transfer of individual patient knowledge, promote a collaborative approach to patient care, facilitate continuity of care and build confidence from both medical and patient perspectives. Including patients in decision‐making processes around transition services will encourage youth‐focused service developments that will help achieve optimal outcomes in young people with chronic illness.

A qualitative study of action plans for asthma.

Abstract Objectives: To investigate the perspectives of patients with asthma on the use of an action plan and the implementation of this plan during an asthma attack that culminated in a visit to an emergency department. Design: Qualitative study. Setting: Tertiary teaching hospital, suburban hospital, and rural hospital. Participants: 62 patients aged 18 to 69 years who presented to an emergency department with asthma over a two month period. Results: 29 participants described having action plans given to them by their doctors. Most patients with action plans reinterpreted their plan from the perspective of their own experiences with asthma. 33 patients did not have an action plan, the most common reason being that they had not been given one by their doctor. Some occupational groups were significantly less likely to have been given an action plan by their doctor than others. Most patients with an action plan found them useful for management of their asthma. Conclusions: Action plans were viewed positively by patients. Participants modified their prescribed plan according to their experience of asthma. To facilitate the implementation of a prescribed action plan, doctors need to acknowledge and include the patients personal experience of their disease. What is already known on this topic Action plans for the self management of asthma are standard and have been shown to improve patient outcomes and to protect against death from asthma when provided in written form Factors that enable patients with asthma to implement an action plan and their perspectives on the use of such plans have not been explored in an individual context What this study adds Most patients with action plans found them useful Most patients modified their plans according to their perceptions of severity and likely disease outcome Clinicians must engage with a patients experience of asthma to facilitate the use of an action plan

Induction of T ‘regulatory’ cells by standardized house dust mite immunotherapy: an increase in CD4+CD25+ interleukin‐10+ T cells expressing peripheral tissue trafficking markers

Background Clinically effective subcutaneous allergen‐specific immunotherapy (SIT) is associated with altered circulating T cell cytokine production and altered local cytokine responses with increased IL‐10 following allergen challenge in target organs.

Haploinsufficiency of the NF-κB1 Subunit p50 in Common Variable Immunodeficiency

Common variable immunodeficiency (CVID), characterized by recurrent infections, is the most prevalent symptomatic antibody deficiency. In ∼90% of CVID-affected individuals, no genetic cause of the disease has been identified. In a Dutch-Australian CVID-affected family, we identified a NFKB1 heterozygous splice-donor-site mutation (c.730+4A>G), causing in-frame skipping of exon 8. NFKB1 encodes the transcription-factor precursor p105, which is processed to p50 (canonical NF-κB pathway). The altered protein bearing an internal deletion (p.Asp191_Lys244delinsGlu; p105ΔEx8) is degraded, but is not processed to p50ΔEx8. Altered NF-κB1 proteins were also undetectable in a German CVID-affected family with a heterozygous in-frame exon 9 skipping mutation (c.835+2T>G) and in a CVID-affected family from New Zealand with a heterozygous frameshift mutation (c.465dupA) in exon 7. Given that residual p105 and p50—translated from the non-mutated alleles—were normal, and altered p50 proteins were absent, we conclude that the CVID phenotype in these families is caused by NF-κB1 p50 haploinsufficiency.

Peripheral lung function in patients with stable and unstable asthma

BACKGROUND Exacerbations of asthma are thought to be caused by airflow obstruction resulting from airway inflammation, bronchospasm, and mucus plugging. Histologic evidence suggests the small airways, including acinar air spaces, are involved; however, this has not been corroborated in vivo by measurements of peripheral small-airway function. OBJECTIVE We sought to determine whether asthma severity is linked to small-airway function, particularly in patients with acute severe asthma. METHODS Eighteen subjects admitted for an asthma exacerbation underwent lung function testing, including measures of acinar ventilation heterogeneity (S(acin)) and conductive ventilation heterogeneity (S(cond)) using the multiple-breath nitrogen washout. Treatment requirement was defined according to Global Initiative for Asthma scores. Data were compared with those obtained in 19 patients with stable asthma. RESULTS For the asthma exacerbation group, the median FEV1 was 59% of predicted value (95% CI, 45% to 75% of predicted value), the median S(cond) value was 185% of predicted value (95% CI, 119% to 245% of predicted value), and the median S(acin) value was 225% of predicted value (95% CI, 143% to 392% of predicted value). FEV1 (percent predicted) was correlated with S(acin) (percent predicted) values (Spearman rho = -0.67, P = .006) but not with S(cond) (percent predicted) values (P > .1). The Global Initiative for Asthma score was significantly related to S(acin) (percent predicted) (Spearman rho = 0.59, P = .016) but not to S(cond) (percent predicted) values (P > .1). The unstable group was characterized by considerably lower forced vital capacity (P < .001) and higher S(cond) (P = .001) values than the unstable group. In a subgroup of 11 unstable patients who could be reviewed after 4 weeks, FEV1, forced vital capacity, S(acin), and S(cond) values showed marked improvements. CONCLUSION Our findings suggest that unstable asthma is characterized by a combined abnormality in the acinar and conductive lung zones, both of which are partly reversible. Functional abnormality in the acinar lung zone in particular showed a direct correlation with airflow obstruction and treatment requirement in patients with acute severe asthma.

Allergen immunotherapy: current and new therapeutic strategies

Allergic individuals respond to an environmental allergen encounter by producing T-cell cytokines, predominantly IL-4 and IL-5, which in turn drive the production of allergen-specific IgE antibodies and recruitment of an eosinophil-rich inflammatory infiltrate. Allergen-specific immunotherapy (SIT) involves the repeated injection of the allergen to specifically downregulate this predominantly Th2-type immune response. SIT is a clinically proven effective treatment for allergic diseases, including rhinoconjunctivitis and asthma. However, despite having been in clinical practice since early this century, its use remains empirical. Best practice protocols are based on clinical experience and include recommendations for selecting patients for treatment, SIT regimes and avoidance of adverse events. More rational and safer SIT regimes will result from new insights into the underlying immune mechanisms for allergic disease, in particular the critical role of helper T-cells in orchestrating this response. The development of recombinant techniques for producing purified allergens and allergen derivatives has led to a dramatic improvement in the ability to standardise allergen preparations and to develop novel vaccines for allergy treatment. Potential vaccines include short peptides based on dominant T-cell epitopes of allergens, allergen fragments and mutant allergens. All of these preparations are designed to target T-cells without binding IgE and inducing local and systemic side effects. Additional strategies under consideration include DNA vaccines and fusion protein constructs incorporating immunomodulatory elements such as bacterial cell proteins, cytokines and immunostimulatory sequences of DNA. Different forms of allergens are being evaluated for the more practical mucosal administration of allergy vaccines. The identification of recombinant allergens suitable for diagnostic use and the development of reliable laboratory assays, based on T-cell function to monitor clinical efficacy of SIT, are important practical outcomes from this research.

Chlorhexidine anaphylaxis: a case report and review of the literature.

A 25-year-old man presented for assessment after an episode of anaphylaxis following insertion of a urethral catheter. He required intermittent dilatation of a urethral stricture after a previous pelvic fracture. Six months earlier he had developed an itchy rash minutes after urethral catheterization under local anaesthetic, which subsided over some hours. On this occasion, a catheter was inserted after infiltration of the urethra with lignocaine 2% with chlorhexidine 0.05% (Pharmacia, Bentley, WA, Australia). Within minutes, his blood pressure fell to 90/60 and he developed a generalized pruritic rash, wheeze and dizziness. He was treated with nebulized salbutamol, intravenous hydrocortisone and subcutaneous adrenaline. He recovered without further incident and was subsequently discharged from hospital.

Longitudinal decline in lung function in patients with primary immunoglobulin deficiencies

clinical symptoms in 90%. The variable disease penetrance within a given pedigree can only be explained by a ‘‘second signal.’’ In our patient the nature of this second signal was shown not to be one of the known genes involved in hemophagocytosis. Once intravenous immune globulin and prednisone were started, ferritin and sIL-2R levels did not completely normalize (ferritin, 600-750 mg/L [upper limit of normal, 350 mg/L]; sIL-2R, 4320 U/mL [upper limit of normal, 2400 U/mL]), even after almost 3 years of follow-up. Hemophagocytosis was detected in neither bone marrow smears nor in spleen and lymph node biopsy specimens. Clinically, the patient fulfilled the diagnosis of hemophagocytic lymphohistiocytosis but was not treated accordingly. The hemophagocytic lymphohistiocytosis parameters (ie, blood cell counts, ferritin, lactate dehydrogenase, sIL-2R, and triglycerides) were considered to be triggered by the pneumonia. The hypoimmunoglobulinemia and defective immunization responses were most compatible with CVID and highly unusual for ALPS. Increased susceptibility to malignancy, particularly hematological malignancy, is the most worrying consequence of ALPS. Lymphoma develops in about 10% of patients, and the relative risks of (non)Hodgkin lymphoma are 15to 50-fold, respectively. Also, patients who have CVID and granulomatous or lymphocytic interstitial lung disease are at high risk for early mortality and B-cell lymphomas. The absence of an increased risk among relatives suggests that the increased cancer morbidity in patients with CVID is related to the immunodeficiency per se rather than to specific genetic traits shared with their relatives. Whether the risk of lymphoproliferative malignancy in our family is increased remains uncertain. The grandfather has died from a mucosa-associated lymphoid tissue lymphoma but was healthy until he presented at old age. We do not know whether he carried the same FAS mutation. In conclusion, mutations in FAS (TNFRSF6) might not only result in clinical ALPS but also in hypogammaglobulinemia and reduced reactivity on immunization, which is defined as CVID. Similar phenotypic overlap was most recently suggested in a study including patients with ALPS and CVID, some of whom were carrying a FAS mutation. Our patient adds to this complex overlap syndrome, presenting with CVID and features of hemophagocytosis, whereas his FAS-mutated family members were without any clinical disease. Taco W. Kuijpers, MD, PhD Paul A. Baars, PhD Daan J. aan de Kerk, MD Machiel H. Jansen Natasja Dors, MD Rene A. W. van Lier, MD, PhD Steven T. Pals, MD, PhD

Nut allergy prevalence and differences between Asian-born children and Australian-born children of Asian descent: a state-wide survey of children at primary school entry in Victoria, Australia

Asian infants born in Australia are three times more likely to develop nut allergy than non‐Asian infants, and rates of challenge‐proven food allergy in infants have been found to be unexpectedly high in metropolitan Melbourne. To further investigate the risk factors for nut allergy, we assessed the whole‐of‐state prevalence distribution of parent‐reported nut allergy in 5‐year‐old children entering school.

Inhaler device technique can be improved in older adults through tailored education: findings from a randomised controlled trial

Aim:To investigate the effects of inhaler device technique education on improving inhaler technique in older people with asthma.Methods:In a randomised controlled trial, device technique education was provided to a sample of 123 adults aged >55 years who had a doctor diagnosis of asthma. The active education group received one-on-one technique coaching, including observation, verbal instruction and physical demonstration at baseline. The passive group received a device-specific instruction pamphlet only. Inhaler technique, including the critical steps for each device type, was assessed and scored according to Australian National Asthma Council (NAC) guidelines. Device technique was scored objectively at baseline and again at 3 and 12 months post education.Results:The majority of participants demonstrated poor technique at baseline. Only 11 (21%) of the active intervention group and 7 (16%) of the passive group demonstrated 100% correct technique. By 3 months 26 (48%) of the active group achieved adequate technique. Improvement in technique was observed in the active group at 3 months (P<0.001) and remained significant at 12 months (P<0.001). No statistically significant improvement was observed in the passive group.Conclusion:The provision of active device technique education improves device technique in older adults. Passive education alone fails to achieve any improvement in device technique.