A de novo paradigm for male infertility.

De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations are classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes (p-value = 1.00 × 10-5) in infertile men compared to controls. Additionally, we detected a significant increase in predicted pathogenic de novo missense mutations affecting missense-intolerant genes (p-value = 5.01 × 10-4) in contrast to predicted benign de novo mutations. One gene we identify, RBM5, is an essential regulator of male germ cell pre-mRNA splicing and has been previously implicated in male infertility in mice. In a follow-up study, 6 rare pathogenic missense mutations affecting this gene are observed in a cohort of 2,506 infertile patients, whilst we find no such mutations in a cohort of 5,784 fertile men (p-value = 0.03). Our results provide evidence for the role of de novo mutations in severe male infertility and point to new candidate genes affecting fertility.

Intervertebral disc degeneration and regeneration: a motion segment perspective.

Back and neck pain have become primary reasons for disability and healthcare spending globally. While the causes of back pain are multifactorial, intervertebral disc degeneration is frequently cited as a primary source of pain. The annulus fibrosus (AF) and nucleus pulposus (NP) subcomponents of the disc are common targets for regenerative therapeutics. However, disc degeneration is also associated with degenerative changes to adjacent spinal tissues, and successful regenerative therapies will likely need to consider and address the pathology of adjacent spinal structures beyond solely the disc subcomponents. This review summarises the current state of knowledge in the field regarding associations between back pain, disc degeneration, and degeneration of the cartilaginous and bony endplates, the AF-vertebral body interface, the facet joints and spinal muscles, in addition to a discussion of regenerative strategies for treating pain and degeneration from a whole motion segment perspective.

The "PPI Hawker": an innovative method for patient and public involvement (PPI) in health research.

BACKGROUND: Patient and Public Involvement (PPI) in health research entails doing research 'with' the public. Successful PPI requires a diversity of patients' perspectives and experiences. In Singapore, including the public's voice in research is still in its infancy and different ways of involving the public have to be explored.Our aims were to describe a PPI initiative that enables members of the public to share their ideas and opinions about health research, and to assess the feasibility, accessibility and utility of the initiative. METHODS: Building on the concept of the PPI Café used in the west we designed a "PPI Hawker" for Singapore. Here Hawker Centres rather than cafes are used frequently for eating and socialising, providing a one-stop destination for a wide section of society. The PPI facilitators approached people sitting at tables and joined them to discuss questions of relevance to a local research study. Observations and reflexive field notes were used to evaluate the "PPI Hawker's" feasibility, acceptability and utility in the Singaporean community. RESULTS: In three "PPI Hawkers" we approached 96 people and 72 (75%) engaged in discussions about the design of a population-based research study. The majority (75%) of participants willingly discussed all of the questions posed to them by the researchers, indicating the feasibility of PPI. The PPI participants came from the three major ethnic groups in Singapore and appeared to be broad in age, suggesting "PPI Hawkers" are easily accessible. Both participants and researchers recognised the utility of the "PPI Hawker", reflecting on people's willingness to talk about the research issues, engaging in informative conversations and posing relevant questions. CONCLUSION: The "PPI Hawkers" succeeded in engaging the public in conversations about a local population-based study. The public brought to the researchers' attention a variety of previously unheard perspectives about the research. Each event fostered connectivity between professionals and the public, generating among researchers a more positive perception of the power of public involvement."PPI Hawkers" provide an opportunity for co-informed conduct of research studies with diverse members of the public. They create a focus within a community setting for researchers to engage with the public. The resources needed (costs and preparatory time) are relatively few. Not only do "PPI Hawkers" have potential in Singapore, but also for the rest of Asia.

Effectiveness of self-management interventions in young adults with type 1 and 2 diabetes: a systematic review and meta-analysis.

AIM: Diabetes in young adulthood has been associated with poor outcomes. Self-management is fundamental to good diabetes care, and self-management interventions have been found to improve outcomes in older adults. We performed a systematic review and meta-analysis to assess the effectiveness of self-management interventions in young adults (aged 15-39 years) with type 1 or type 2 diabetes. METHODS: We searched five databases and two clinical trial registries from 2003 to February 2019, without language restrictions. We included randomized controlled trials (RCTs) comparing the effectiveness of self-management interventions with usual care or enhanced usual care in young adults. Outcomes of interest included clinical outcomes, psychological health, self-care behaviours, diabetes knowledge and self-efficacy. Pairwise meta-analysis was conducted using a random effects model and quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. We followed Cochrane gold standard systematic review methodology and reported this systematic review according to PRISMA guidelines. The protocol was registered with PROSEPRO (CRD42018110868). RESULTS: In total, 13 studies (1002 participants) were included. Meta-analysis showed no difference between self-management interventions and controls in post-intervention HbA1c levels, BMI, depression, diabetes-related distress, overall self-care, diabetes knowledge and self-efficacy. Quality of evidence ranged from very low to moderate due to study limitations, inconsistency and imprecision. CONCLUSIONS: Current self-management interventions did not improve outcomes in young adults with diabetes. Our findings, which contrast with those from systematic reviews in older adults, highlight the need for the development of more effective interventions for young adults with diabetes.

Attitudes and perception of influenza vaccines among older people in Singapore: A qualitative study.

BACKGROUND: Despite recommendations for influenza vaccination of people aged 65 and above, uptake rate of influenza vaccines remains low. This study aims to understand barriers and motivators behind older adult's decision on influenza vaccination. METHODS: Face to face interviews with participants aged 65 and above were conducted and audio recorded in Geylang polyclinic in Singapore. Thematic content analysis was used to organise the data. RESULTS: 15 older adults were interviewed, aged between 66 and 85 years old. 6 were vaccine refusers, 3 defaulters and 6 acceptors. A perceived lack of vulnerability, fear of side effects, and trivialisation of influenza were common reasons for not taking the vaccine. Encouragement from family and friends, travel and previous positive vaccination experiences were motivators for getting vaccinated. Healthcare workers played a role in influencing many of the participants' decision-making. Common misconceptions included vaccines considered as necessary only before travel and as a cure rather than prevention. Most participants exhibited ambivalence, giving reasons both for and against vaccine uptake. DISCUSSION: Most older adults do not perceive influenza as a potentially serious disease nor trust in influenza vaccines' efficacy. Misconceptions played a significant role in vaccine decline. Novel findings include the importance of the family unit in decision making, prioritization of chronic health problems over vaccination and misconception that vaccines are only needed when travelling out of country. Healthcare workers and family members appear to be important influencers in the decision making of older adults and should be actively engaged in future health promotion initiatives.

Multiscale and multimodal structure-function analysis of intervertebral disc degeneration in a rabbit model.

OBJECTIVES: The objective of this study was to perform a quantitative analysis of the structural and functional alterations in the intervertebral disc during in vivo degeneration, using emerging tools that enable rigorous assessment from the microscale to the macroscale, as well as to correlate these outcomes with noninvasive, clinically relevant imaging parameters. DESIGN: Degeneration was induced in a rabbit model by puncturing the annulus fibrosus (AF) with a 16-gauge needle. 2, 4, 8, and 12 weeks following puncture, degenerative changes in the discs were evaluated via magnetic resonance imaging (MRI), whole motion segment biomechanics, atomic force microscopy, histology and polarized light microscopy, immunohistochemistry, biochemical content, and second harmonic generation imaging. RESULTS: Following puncture, degeneration was evident through marked changes in whole disc structure and mechanics. Puncture acutely compromised disc macro and microscale mechanics, followed by progressive stiffening and remodeling. Histological analysis showed substantial anterior fibrotic remodeling and osteophyte formation, as well as an overall reduction in disc height, and disorganization and infolding of the AF lamellae into the NP space. Increases in NP collagen content and aggrecan breakdown products were also noted within 4 weeks. On MRI, NP T2 was reduced at all post-puncture time points and correlated significantly with microscale indentation modulus. CONCLUSION: This study defined the time dependent changes in disc structure-function relationships during IVD degeneration in a rabbit annular injury model and correlated degeneration severity with clinical imaging parameters. Our findings identified AF infolding and occupancy of the space as a principle mechanism of disc degeneration in response to needle puncture, and provide new insights to direct the development of novel therapeutics.

Exploring what motivates and sustains support group engagement amongst young people with allergies: A qualitative study.

BACKGROUND: Positive self-care behaviours are more likely in young people who engage with allergy support groups, but reasons for this association are not well understood. OBJECTIVES: This study explored how and why young people engage with allergy support groups to identify what activities and resources are beneficial. METHODS: In-depth, semistructured interviews were conducted with young people aged 12-21 years who reported engaging with allergy support groups (in person or online). Interviews were audiotaped, transcribed verbatim and analysed using thematic content analysis. RESULTS: The 21 participants had a range of allergies; initially, most joined support groups on suggestion of their parent/carer although older participants sought groups independently. Feeling included and sharing experiences with people with similar problems/challenges were highly valued. Through membership, young people reported improved self-esteem and confidence in both managing their allergies and lives generally. Information, such as allergy alerts and hard-hitting video campaigns, were reported to positively influence adherence to self-care behaviours such as carrying medication. Participants wanted greater availability of allergy support groups, and higher profiles in health care and educational settings, as well as through social media. CONCLUSIONS AND CLINICAL RELEVANCE: Participants valued the psychological and practical support of networking with others with allergies, and described how membership improved their confidence. This study also provides insight into the ways support groups improve young people's adherence to medical advice and positive self-care behaviours; participants responded well to hard-hitting video campaigns which appeared to emphasize the severity and susceptibility of anaphylaxis. Participants identified the need for more active promotion of support groups amongst young people and their clinicians, as well as making them available in more localities.

Allergy in the elderly: A case note review of referrals to an adult allergy clinic.

The UK population is ageing and we can expect more referrals to allergy clinics for this age group. 16% of patients to our clinic are aged >60. Compared to younger patients, 3 times as many referrals were for angioedema. Overall, allergy was excluded in 79% of cases. 15% were diagnosed with previously unrecognised allergies, while allergic disease was confirmed in 6%, enabling optimised management. While the differential diagnosis of allergic conditions is wider in older people, assessment in the allergy clinic is helpful and adds value.

In Vitro Maturation and In Vivo Integration and Function of an Engineered Cell-Seeded Disc-like Angle Ply Structure (DAPS) for Total Disc Arthroplasty.

Total disc replacement with an engineered substitute is a promising avenue for treating advanced intervertebral disc disease. Toward this goal, we developed cell-seeded disc-like angle ply structures (DAPS) and showed through in vitro studies that these constructs mature to match native disc composition, structure, and function with long-term culture. We then evaluated DAPS performance in an in vivo rat model of total disc replacement; over 5 weeks in vivo, DAPS maintained their structure, prevented intervertebral bony fusion, and matched native disc mechanical function at physiologic loads in situ. However, DAPS rapidly lost proteoglycan post-implantation and did not integrate into adjacent vertebrae. To address this, we modified the design to include polymer endplates to interface the DAPS with adjacent vertebrae, and showed that this modification mitigated in vivo proteoglycan loss while maintaining mechanical function and promoting integration. Together, these data demonstrate that cell-seeded engineered discs can replicate many characteristics of the native disc and are a viable option for total disc arthroplasty.

An approach for the identification of exemplar sites for scaling up targeted field observations of benthic biogeochemistry in heterogeneous environments.

Continental shelf sediments are globally important for biogeochemical activity. Quantification of shelf-scale stocks and fluxes of carbon and nutrients requires the extrapolation of observations made at limited points in space and time. The procedure for selecting exemplar sites to form the basis of this up-scaling is discussed in relation to a UK-funded research programme investigating biogeochemistry in shelf seas. A three-step selection process is proposed in which (1) a target area representative of UK shelf sediment heterogeneity is selected, (2) the target area is assessed for spatial heterogeneity in sediment and habitat type, bed and water column structure and hydrodynamic forcing, and (3) study sites are selected within this target area encompassing the range of spatial heterogeneity required to address key scientific questions regarding shelf scale biogeochemistry, and minimise confounding variables. This led to the selection of four sites within the Celtic Sea that are significantly different in terms of their sediment, bed structure, and macrofaunal, meiofaunal and microbial community structures and diversity, but have minimal variations in water depth, tidal and wave magnitudes and directions, temperature and salinity. They form the basis of a research cruise programme of observation, sampling and experimentation encompassing the spring bloom cycle. Typical variation in key biogeochemical, sediment, biological and hydrodynamic parameters over a pre to post bloom period are presented, with a discussion of anthropogenic influences in the region. This methodology ensures the best likelihood of site-specific work being useful for up-scaling activities, increasing our understanding of benthic biogeochemistry at the UK-shelf scale.

Oxygen dynamics in shelf seas sediments incorporating seasonal variability.

Shelf sediments play a vital role in global biogeochemical cycling and are particularly important areas of oxygen consumption and carbon mineralisation. Total benthic oxygen uptake, the sum of diffusive and faunal mediated uptake, is a robust proxy to quantify carbon mineralisation. However, oxygen uptake rates are dynamic, due to the diagenetic processes within the sediment, and can be spatially and temporally variable. Four benthic sites in the Celtic Sea, encompassing gradients of cohesive to permeable sediments, were sampled over four cruises to capture seasonal and spatial changes in oxygen dynamics. Total oxygen uptake (TOU) rates were measured through a suite of incubation experiments and oxygen microelectrode profiles were taken across all four benthic sites to provide the oxygen penetration depth and diffusive oxygen uptake (DOU) rates. The difference between TOU and DOU allowed for quantification of the fauna mediated oxygen uptake and diffusive uptake. High resolution measurements showed clear seasonal and spatial trends, with higher oxygen uptake rates measured in cohesive sediments compared to the permeable sediment. The significant differences in oxygen dynamics between the sediment types were consistent between seasons, with increasing oxygen consumption during and after the phytoplankton bloom. Carbon mineralisation in shelf sediments is strongly influenced by sediment type and seasonality.

Comparing benthic biogeochemistry at a sandy and a muddy site in the Celtic Sea using a model and observations.

Results from a 1D setup of the European Regional Seas Ecosystem Model (ERSEM) biogeochemical model were compared with new observations collected under the UK Shelf Seas Biogeochemistry (SSB) programme to assess model performance and clarify elements of shelf-sea benthic biogeochemistry and carbon cycling. Observations from two contrasting sites (muddy and sandy) in the Celtic Sea in otherwise comparable hydrographic conditions were considered, with the focus on the benthic system. A standard model parameterisation with site-specific light and nutrient adjustments was used, along with modifications to the within-seabed diffusivity to accommodate the modelling of permeable (sandy) sediments. Differences between modelled and observed quantities of organic carbon in the bed were interpreted to suggest that a large part (>90%) of the observed benthic organic carbon is biologically relatively inactive. Evidence on the rate at which this inactive fraction is produced will constitute important information to quantify offshore carbon sequestration. Total oxygen uptake and oxic layer depths were within the range of the measured values. Modelled depth average pore water concentrations of ammonium, phosphate and silicate were typically 5-20% of observed values at the muddy site due to an underestimate of concentrations associated with the deeper sediment layers. Model agreement for these nutrients was better at the sandy site, which had lower pore water concentrations, especially deeper in the sediment. Comparison of pore water nitrate with observations had added uncertainty, as the results from process studies at the sites indicated the dominance of the anammox pathway for nitrogen removal; a pathway that is not included in the model. Macrofaunal biomasses were overestimated, although a model run with increased macrofaunal background mortality rates decreased macrofaunal biomass and improved agreement with observations. The decrease in macrofaunal biomass was compensated by an increase in meiofaunal biomass such that total oxygen demand remained within the observed range. The permeable sediment modification reproduced some of the observed behaviour of oxygen penetration depth at the sandy site. It is suggested that future development in ERSEM benthic modelling should focus on: (1) mixing and degradation rates of benthic organic matter, (2) validation of benthic faunal biomass against large scale spatial datasets, (3) incorporation of anammox in the benthic nitrogen cycle, and (4) further developments to represent permeable sediment processes.

An emerging zoonotic clone in the Netherlands provides clues to virulence and zoonotic potential of Streptococcus suis.

Streptococcus suis is a zoonotic swine pathogen and a major public health concern in Asia, where it emerged as an important cause of bacterial meningitis in adults. While associated with food-borne transmission in Asia, zoonotic S. suis infections are mainly occupational hazards elsewhere. To identify genomic differences that can explain zoonotic potential, we compared whole genomes of 98 S. suis isolates from human patients and pigs with invasive disease in the Netherlands, and validated our observations with 18 complete and publicly available sequences. Zoonotic isolates have smaller genomes than non-zoonotic isolates, but contain more virulence factors. We identified a zoonotic S. suis clone that diverged from a non-zoonotic clone by means of gene loss, a capsule switch, and acquisition of a two-component signalling system in the late 19th century, when foreign pig breeds were introduced. Our results indicate that zoonotic potential of S. suis results from gene loss, recombination and horizontal gene transfer events.

Rapid detection of Streptococcus uberis in raw milk by loop-mediated isothermal amplification.

A loop-mediated isothermal amplification (LAMP) method to detect Streptococcus uberis in raw milk was developed and evaluated. Three genes (sodA, pauA, cpn60) were assessed for their suitability as targets in LAMP. The analytical sensitivity was 120, 120, and 12 fg per assay for the sodA, pauA, and cpn60 assays, respectively, with a detectable signal within 8 min for the highest concentration (12ng/assay) and ~60 min for the lowest concentrations. The LAMP assays correctly identified 7 Strep. uberis strains among a set of 83 mastitis pathogens. To enable DNA isolation from raw milk, a new method was used in which a pretreatment with a cocktail of lysing enzymes was performed before an established procedure. This method resulted in an analytical sensitivity of 48 cfu/assay for the sodA LAMP assay using raw milk spiked with Strep. uberis, corresponding to 2.4×10(4) cfu/mL milk. For raw milk samples from cows experimentally infected with Strep. uberis, results of enumeration were largely reflected by results of LAMP. Evaluation of the sodA LAMP assay with 100 raw milk field samples, of which 50 were Strep. uberis culture-negative and 50 Strep. uberis culture-positive, showed that the assay had a diagnostic sensitivity of 96.0% and a diagnostic specificity of 96.0%. In conclusion, the described LAMP assay may offer a simple alternative for convenient and sensitive detection of S. uberis in raw milk, provided a compatible rapid DNA isolation procedure is available.

Does written emotional disclosure improve the psychological and physical health of caregivers? A systematic review and meta-analysis.

There are 5.8 million caregivers providing support to the infirm, disabled or elderly in the United Kingdom. Caregivers experience adverse physical and mental health outcomes and increased mortality. Low cost, effective interventions are needed to increase the wellbeing of caregivers. Written emotional disclosure (WED) has been shown to improve health in a range of populations. This systematic review and meta-analysis aimed to establish whether WED improves the psychological and physical health of caregivers. Searches were conducted in Medline, EMBASE, CINAHL, BNI, PsycINFO, Cochrane Library from 1986 to 2015. Ten trials investigating WED (625 participants) met the inclusion criteria. Results from four studies (n = 118) indicated that WED reduces trauma (SMD = -0.46, 95% CI -0.82, -0.09). Data from three studies (n = 102) suggest that WED improves general psychological health (SMD = -0.46, 95% CI -0.86, -0.06). There was no evidence that WED improves depression, anxiety, physical symptoms, quality of life or burden. Observations suggest WED may be more effective for caregivers of less than 5 years. Studies were highly heterogeneous in regards to caregiver age, relationship to care recipient, impairment of care recipient, follow up period and outcome measures, with high or unclear bias often observed. More rigorous RCTs, with clearly described interventions and standardised outcome measures, are needed to confirm these findings.

Nonpharmacological interventions aimed at modifying health and behavioural outcomes for adults with asthma: a critical review.

Evidence suggests that living with asthma is linked with psychological and behavioural factors including self-management and treatment adherence, and therefore, there is a reasonable hypothesis that nonpharmacological treatments may improve health outcomes in people living with this condition. A systematic review of randomized controlled trials (RCTs) of nonpharmacological interventions for adults with asthma was designed. Databases searched included The Cochrane Airways Group Register of trials, CENTRAL and Psychinfo. The literature search was conducted until May 2014. Twenty-three studies met the inclusion criteria and were organized into four groups: relaxation-based therapies (n = 9); mindfulness (n = 1), biofeedback techniques (n = 3); cognitive behavioural therapies (CBT) (n = 5); and multicomponent interventions (n = 5). A variety of outcome measures were used, even when trials belonged to the same grouping, which limited the ability to conduct meaningful meta-analyses. Deficiencies in the current evidence base, notably trial heterogeneity, means that application to clinical practice is limited and clear guidelines regarding the use of nonpharmacological therapies in asthma is limited. Relaxation and CBT, however, appear to have a consistent positive effect on asthma-related quality of life and some psychological outcomes, and lung function (relaxation only). Future trials should be informed by previous work to harmonize the interventions under study and outcome measures used to determine their effectiveness; only then will meaningful meta-analyses inform clinical practice.

What proportion of adult allergy referrals to secondary care could be dealt with in primary care by a GP with special interest?

BACKGROUND: The concept of a General Practitioner with Special Interest (GPwSI) was first proposed in the 2000 National Health Service Plan, as a way of providing specialised treatment closer to the patient's home and reducing hospital waiting times. Given the patchy and inadequate provision of allergy services in the UK the introduction of GPwSIs might reduce the pressure on existing specialist services. OBJECTIVES: This study assessed what proportion of referrals to a specialist allergy clinic could be managed in a GPwSI allergy service with a predefined range of facilities and expertise (accurate diagnosis and management of allergy; skin prick testing; provision of advice on allergen avoidance; ability to assess suitability for desensitisation). METHODS: 100 consecutive GP referrals to a hospital allergy clinic were reviewed to determine whether patients could be seen in a community-based clinic led by a general practitioner with special interest (GPwSI) allergy. The documentation relating to each referral was independently assessed by three allergy specialists. The referrals were judged initially on the referral letter alone and then re-assessed with the benefit of information summarised in the clinic letter, to determine whether appropriate triage decisions could be made prospectively. The proportion of referrals suitable for a GPwSI was calculated and their referral characteristics identified. RESULTS: 29 % referrals were judged unanimously appropriate for management by a GPwSI and an additional 30 % by 2 of the 3 reviewers. 18 % referrals were unsuitable for a GPwSI service because of the complexity of the presenting problem, patient co-morbidity or the need for specialist knowledge or facilities. CONCLUSIONS AND CLINICAL RELEVANCE: At least a quarter, and possibly half, of allergy referrals to our hospital-based service could be dealt with in a GPwSI clinic, thereby diversifying the patient pathway, allowing specialist services to focus on more complex cases and reducing the waiting time for first appointments.

Role of glucose and CcpA in capsule expression and virulence of Streptococcus suis.

Streptococcus suis is one of the most important pathogens in pigs and is also an emerging zoonotic agent. After crossing the epithelial barrier, S. suis causes bacteraemia, resulting in meningitis, endocarditis and bronchopneumonia. Since the host environment seems to be an important regulatory component for virulence, we related expression of virulence determinants of S. suis to glucose availability during growth and to the sugar metabolism regulator catabolite control protein A (CcpA). We found that expression of the virulence-associated genes arcB, representing arcABC operon expression, cps2A, representing capsular locus expression, as well as sly, ofs, sao and epf, differed significantly between exponential and early stationary growth of a highly virulent serotype 2 strain. Deletion of ccpA altered the expression of the surface-associated virulence factors arcB, sao and eno, as well as the two currently proven virulence factors in pigs, ofs and cps2A, in early exponential growth. Global expression analysis using a cDNA expression array revealed 259 differentially expressed genes in early exponential growth, of which 141 were more highly expressed in the CcpA mutant strain 10ΔccpA and 118 were expressed to a lower extent. Interestingly, among the latter genes, 18 could be related to capsule and cell wall synthesis. Correspondingly, electron microscopy characterization of strain 10ΔccpA revealed a markedly reduced thickness of the capsule. This phenotype correlated with enhanced binding to porcine plasma proteins and a reduced resistance to killing by porcine neutrophils. Taken together, our data demonstrate that CcpA has a significant effect on the capsule synthesis and virulence properties of S. suis.

Measuring asthma-specific quality of life: structured review.

Measuring quality of life (QoL) has become an increasingly important dimension of assessing patient well-being and drug efficacy. As there are now several asthma QoL questionnaires to choose from, it is important to appreciate their strengths and weaknesses. To assist in this choice, we have reviewed the existing questionnaires in a structured way. Information relating to the conceptual and measurement model, reliability, validity, interpretability, burden, administration format and translations was extracted from the published literature. The instruments differ in almost all criteria considered, and therefore it cannot be assumed that they measure the same thing. We recommend the selection of questionnaires that are designed only for asthma and that do not assess symptoms as part of QoL. Only two of the questionnaires reviewed fulfill these requirements: the Sydney Asthma QoL Questionnaire (AQLQ-S) and the Living with Asthma Questionnaire (LWAQ). However, for multinational studies, it may be convenient or practical to use questionnaires that have been linguistically validated in many languages (AQLQ-J, SGRQ). It remains unclear which of these questionnaires best reflects patient perceptions of QoL. Our review did not involve patients, so for the time being choosing from existing questionnaires requires a compromise based on the rigor of the development process and the target patient group.