Year‐in‐review 2010: Asthma, COPD, cystic fibrosis and airway biology (2011)

Respiratory diseases are estimated to affect a billion people around the world, and account for 12 million deaths a year. In order to raise awareness of respiratory conditions, the Forum of International Respiratory Societies (FIRS), which includes the Asia Pacific Society of Respirology, declared 2010 the Year of the Lung.1 One of the highlight events of the year was World Spirometry Day on October 14, when over 100 000 free spirometry tests were performed at 412 events worldwide. The Year of the Lung also involved intense lobbying of legislative bodies to promote issues such as air quality and anti-tobacco initiatives, and to encourage direction of research funding towards respiratory conditions. One of the important goals of the Year of the Lung was to focus awareness on respiratory research. In this review, we describe important global advances in 2010 in asthma, COPD, cystic fibrosis and airway biology, and highlight the contribution of research in these areas from Respirology. Helen Reddel In 2010, in a series of thought-provoking editorials, pro/con debates and reviews, Respirology provided a forum for discussion about important issues in asthma management. The discussion commenced with a Think Tank Review by Hancox and colleagues,2 which focussed on several ‘inconvenient truths’ about asthma, and linked these to current controversies in areas such as epidemiology, safety of long-acting β2-agonists (LABA) and clinical practice guidelines. Subsequently, in the first of several pro/con debates, O'Byrne and Colice argued, respectively, for and against the proposition that the current stepwise approach to asthma pharmacotherapy in guidelines encourages over-treatment.3 The discussion focussed on factors which currently encourage clinicians to increase medication doses when asthma is not completely controlled rather than considering more basic factors such as poor adherence or poor inhaler technique. The authors emphasized the importance of treating medication changes as therapeutic trials, to avoid an inevitable upward progression of medication use. Discussion about the safety of LABA continued unabated in 2010, with a robust pro/con debate in Respirology about whether more evidence on this topic is needed.4 On the pro side, Drazen, Kazani and Ware argued that the current level of uncertainty about safety was unacceptable, and proposed a randomized controlled trial of 50 000 patients. On the con side, Sears argued that no safety signal was seen when concomitant inhaled corticosteroid use was mandatory. As moderator, Taylor commented that it was unlikely that the outcomes of any further safety study would be regarded as final, and recommended ongoing vigilance for adverse effects of β2-agonists.4 In a third pro/con debate,5 Bardin, as moderator, asked whether allergy still had a role in asthma exacerbations, reminding readers that for much of the 20th century, they were mostly assumed to be caused by allergens. On the pro side, Custovic and Simpson provided evidence of synergistic effects between viruses, atopy and allergen exposure, and argued that previous evidence may have been diluted by the phenotypic heterogeneity of asthma. On the con side, Le Souëf argued that allergy, rather than being causally related to asthma, was a marker for more important deficits in the immune system that allowed respiratory viruses to induce exacerbations. The complexity of the relationships between socioeconomic factors and the prevalence of asthma was demonstrated in a population-based study published in Respirology, in which Chittleborough and colleagues reported that gender interactions varied according to which socioeconomic variable, for example employment, educational status or income, was considered.6 Recent years have seen increasing awareness of the need for use of objective measures in epidemiological studies. The Tennessee Children's Respiratory Initiative, the design of which was reported in Respirology,7 recruited over 650 families during acute viral respiratory illness of infancy. These children will be followed to age 6 years with standardized assessments, to identify modifiable factors important in the development of asthma. One of the challenges in such studies is in the way asthma should be defined. The scale of this issue for paediatric epidemiological studies was highlighted by Van Wonderen and colleagues in a systematic review8 which identified no fewer than 60 definitions of childhood asthma; the choice of definition had a major impact on predictive models for asthma prevalence. Paediatric epidemiological studies often depend on parent-reported wheezing, but wheezing is poorly defined, and the range of human hearing varies among individuals. In Respirology, Habukawa and colleagues9 demonstrated a lack of correlation between airway hyperresponsiveness, spirometry and wheezing sounds, using sound spectography during methacholine challenge. The frequency of both inspiratory and expiratory breath sounds increased during challenge testing and decreased following administration of salbutamol. The importance of objective measures for asthma studies in adults was also highlighted in 2010 by Luks and colleagues;10 following their earlier demonstration that 30% of doctor diagnoses of asthma were incorrect,11 the authors demonstrated that a correct diagnosis could be confirmed in over 90% of patients with a simple bronchodilator reversibility test or single methacholine challenge, even in those taking regular controller medications. For patients presenting primarily with cough, a standard objective measure has been capsaicin challenge,12 which stimulates C-fibre cough receptors. As cough may also be stimulated via rapidly adapting mechanoreceptors, Kamimura and colleagues13 investigated three modes of mechanical stimulation (tracheal compression, neck retroflexion, tuning fork). Induction of an itchy sensation and cough with all tests was significantly more likely in patients reporting phonation-induced cough. Further major work on asthma phenotypes was published in 2010, including a cluster analysis of 726 patients with mild, moderate and severe asthma, published from the Severe Asthma Research Program.14 Eighty per cent of patients were able to be classified into one of five clusters on the basis of just three clinical variables—pre- and post-bronchodilator FEV1% predicted, and age of onset of asthma. Even more interesting will be future work from this programme on predictors of clinical course and response to treatment. The interaction between asthma and obesity is complex. In Respirology, Arshi and colleagues15 studied the relationship between obesity and asthma in children, finding insulin resistance in almost half of the children with allergic asthma but none of the BMI-matched healthy controls, with some interesting patterns emerging in the relationships between insulin resistance and blood levels of several adipokines. With increasing awareness of phenotypic differences in asthma, increasing importance is placed on the identification of predictors of response to different asthma medications, and, as a corollary, on phenotype-based approaches to asthma management. In a novel triple cross-over study, Lemanske and colleagues16 investigated the predictors of response to add-on therapy with LABA, montelukast or higher dose inhaled corticosteroid, for children with persistent asthma who were uncontrolled on inhaled corticosteroids alone. Almost all of the children demonstrated a differential response between treatments, but, contrary to prior assumptions, baseline characteristics mostly failed to predict the most effective treatment for individual patients. Polymorphisms of the β2-adrenoceptor gene did not predict response to add-on LABA in this study. In Respirology, and the impact for β2-adrenoceptor studies of reporting response as a of the reversibility administration of both and rather than as the administration of alone. In Respirology, and provided a clinical on the use of of from research to clinical example of treatment was reported by and who the effects of and on and airway to in adults with cough, or and of the study confirmed that in patients with airway and were by of inhaled of treatment is in the phenotypic marker but have and the of phenotypes over a year in patients with moderate and severe asthma. of patients demonstrated a with for In Respirology, and reported of to with important differences in levels from different of In to clinical of 2010 the of in novel treatment approaches for asthma, with studies further evidence for the importance of of patients and measures in the design of clinical study of in patients with severe identified in asthma exacerbations, that the of asthma with impact on of clinical asthma The demonstration in this study of a also highlighted the need for of for and for to the impact of provided to study as was demonstrated by and colleagues in a approach was by and who the of of for patients with asthma, and reported in quality of and and with In Respirology, provided a of asthma the on a asthma as research was by the in the that is The most with current to be in or treatment of allergic asthma, with fewer for in more or severe is increasing in the and to asthma exacerbations, by their or by their most on for in individual a example of the impact of changes on asthma outcomes was seen during 2010, when and reported that the of in in had to a in paediatric asthma of per for with an increase of per year in the 6 2010 also the of evidence about the impact of even levels of air on for asthma in the need for for asthma in have not been and they a to study of about randomized controlled in such into factors that may to In Respirology, and the impact of the of for asthma in a in The of for acute severe asthma in was with a in the of patients and mechanical and a in and has been as a marker of acute and has been to be a of than in and colleagues the of for the of exacerbations, and reported that the be a marker of of the and As the blood performed in most patients on to includes the is no for this has been as a in respiratory including and colleagues the of in patients with an of the and that levels may predict the response to treatment in patients with acute exacerbations. The is an for and and is to use. As is a for as by is test for the diagnosis of airway and colleagues investigated the of a of an with a diagnosis from the International as a in patients with that the of the with a may be a and of patients a Lung of is as an of of has been demonstrated in patients with as with and colleagues demonstrated that of is with increased during in patients with has to be whether the of cough is a for the development of and colleagues the prevalence of in the of on a in and identified the of in patients with that is a prevalence of in the of in and that is not to the diagnosis of and colleagues reported that cough is an for the development of in in with In the authors recommended that who of this should be regarded as being at for the development of The that as in the for Lung may be for the identification of at of are important for acute of and their prevalence has been reported to from to and colleagues a systematic which the prevalence of respiratory viral in and that viruses are with with the of viruses being in The of viruses may have important therapeutic for of is not with an response in the but also with and colleagues whether and in patients with using and blood reported that an increase in the and and levels may earlier in the airway than in and may the of than blood may be in patients with severe or severe is one of the of and the and colleagues whether or not in adults years was with increased prevalence and of several to were an estimated and any of in the diagnosis was with higher and higher from On some patients are to have fibrosis and In a study of patients with and patients with COPD, and colleagues reported that the had and than the and of the patients had also reported that during for levels of or in patients to be more severe than in patients. and colleagues reported that and are both diseases with major and that they to more than from their the authors also commented that the of prevalence be of and in of both and colleagues reported that may of and increase the of in patients with further studies may be to the for these in whether or is as these are modifiable corticosteroids are in the treatment of acute severe of of and of treatment and one of five patients the most being and colleagues reported in Respirology, for the first of a study of patients who were was in was as as in patients for which is than the of treatment for exacerbations. In an and that the of in patients who inhaled corticosteroids in the further recommended for with a towards treatment in further studies are on the of different to treatment in patients with As is also uncertainty the dose and of corticosteroid treatment for exacerbations, it may be more to to avoid doses per or treatment and in for patients with COPD, for such as may be and more than dose is the current standard of for patients with acute of who not to and bronchodilator treatment. is uncertainty about the of in this trial of with did not in In the of severe airway and have different of and a more heterogeneity and of and in a that the of which to a the of both modes of and may in COPD, a study of 100 patients by and colleagues that the following first treatment with was As in the by and more effective treatment is for One such at was in study by and who in the of patients with persistent controlled of have reported for and quality of at this should not be regarded as an treatment for and colleagues the to an programme for patients with and the often areas of programme and of to With to baseline and in in Respirology, that the test should be or several as is a of the test is important as and colleagues that it be to predict the with the being the and for in order to a to during including have been in patients with and colleagues the effects of during with the on in patients with that it was and did not to clinical outcomes during is and a systematic and on the impact of on patients with were not able to any in quality of is evidence for the of in is an important which will the of this important it be with In the years the cystic fibrosis gene was in have been advances in this The focus on and clinical outcomes and the evidence and of with an for The with the in outcomes and the future have been by and is a awareness of airway and in and children with The clinical measures to both from a clinical and from a research and colleagues may be in the to with a to highlight of with and seen on treatment was this may is as and the evidence for effective in children and is issues such as the of and respiratory affect the quality of the it more to these in in in children have been reported using in children as as years of and the development of dose may in the the frequency of such tests and the clinical further and colleagues that doses are and increase with increasing age in children with and may be higher in children who with With in patients with to be to avoid Lung testing a of clinical in patients with and finding that be to response to including and childhood are The measures resistance of the respiratory system and in the way of from the it as an for airway and response to bronchodilator in and colleagues have that the resistance estimated from as as that estimated from may both be in patients with bronchodilator response may be using and colleagues demonstrated that in children years in children and and colleagues have reported changes in with use of inhaled and with tests as clinical trial to a of challenges including with and which have been investigated and by and a major with increased and for children and adults with and, is to has a with a that between different and an with of For a readers should to a The of to in the to has been with the of levels of that a to the resistance The is for but that have a more of a of has been to increase following to doses of and with increasing in from some patients with the and increasing will be to to in the The treatment for or of of has not been 2010 has seen the of the of randomized controlled different treatment The study demonstrated a in using rather than of inhaled children free of at at therapy using inhaled and for did not the of or with in children with The also reported the of increased in respiratory in the treatment with over the years of the The treatment of using inhaled therapy has a standard of and such as are and are much effective treatment of are being and reported in respiratory from patients with The to identify the from has and colleagues in of the patients who provided were with three of which were with increased and One of the was with increased resistance to and from and colleagues reported in a study of patients one of which was to the with a was over the study, with was with an increased of or is a with and reporting the the that with are likely to be with clinical the clinical of with these clinical status to with such a or the per to the age of important or are factors and are in their clinical studies to these are has been to of in with is and are and and with a of including clinical in a increased with which the in and also failed to from the in a not in about the for increasing resistance and the of as in patients. and reported changes in patterns over years in patients with 6 years and with who the for the of for resistance was seen for over and an increasing prevalence of as as such as and The clinical of of these and has not been and is being and colleagues from the and demonstrated that of from respiratory was with has been as a in patients and colleagues a approach to with the use of to severe persistent in a and colleagues a for and have from the to an with and an increased of airway is also being in and and colleagues a between the of or more respiratory for and increased of for in children and people than years of age with from the at the for in are to be with in patients with and and colleagues have reported an between and respiratory in children with are to have and effects and have been to and in a for the in frequency of reported with has a age of that in the In a study, and colleagues demonstrated between clinical and from from children with that complexity was with and with of and with to both and inhaled studies from respiratory in patients with will more on the of interaction and the effects on outcomes in the a for in and colleagues from the with a of with in to baseline identified factors with the to to poor with such as and allergic and a and in between baseline spirometry and of treatment. that patients at should be more and that further research is to identify and treatment of of As into to for patients with such as and diseases with are and colleagues demonstrated in a study in the to that adults with have higher levels with healthy of The of this and clinical with about the for increased In the that as of the is seen in patients over years with levels may be a marker for Further studies will be to the and with these in the with even with the and have a clinical are to be important in this of the role of and colleagues confirmed in the the previous that of is with in also that were significantly higher and in was in patients who also an that of may the the effects on such as and in the airway is with approaches and including the gene such as are emerging to the basic in to which will the in this and important and areas of research in with areas of studies are currently the standard for systematic identification of of studies have been published this year and are highlighted and performed a in three including current or with and identified a at in the In a study, and a between an single in involved in and likely important in with the or of were published in 2010 and asthma in several novel and on and on the gene on the gene the gene on the gene on and gene on the most was the study by and identified in several such as and the that between the following and the immune system is for of airway this study confirmed a role for for asthma have failed to be in is important to the contribution of a gene to the asthma One such was reported in Respirology by and on in between the and increased of asthma was but in and in the need for to be in studies. The immune response is the first of and is for and of important of is the and of a In this the as a between the and immune and it is likely that significantly to the of both and asthma. year in Respirology, several were published the continued importance of this in both and in from current and with COPD, as as with that the was significantly to from in a study, the that with in but not with of the in a is to to the seen in and the of increased of and also the of in these and that several were all increased in of in was with the marker and was with has been to be of and and is both and a and colleagues that rapidly and of of did not was a role between and The increased of in response to and is a of and asthma. and is to As to these would likely patients. and that of to for 12 with and in that the a in which with a and and decreased not related to of or of has effects on the those with to following could have and colleagues or to prior to to to to and were all by the of the the increased has been to the to the would be interesting to whether could the caused by The identification and of have much in to and the clinical of respiratory such as and more have been as of Even is the identification of such as The of and levels in from patients and current have also been as the were as the of and were levels of and were In a study published this year in Respirology, and the of of the system and also as in and of patients with The system an important role in the and of and to is an important by levels of and were not increased in COPD, levels of and significantly with and but with on the Respiratory One of the more and of airway is the increase in airway of from is increased in but we have of the and investigated whether was involved it has been in and as as and differential of in the and treatment with a did not these the and an of allergic airway to the role of of such as have been to in that between immune and the in the and and are placed to be important in airway In levels are increased by the allergen in a of more this is in the and from patients from allergen a of via including which has also been in asthma. and colleagues that or a in and airway The of gender is an of asthma research for several is a higher of asthma and diseases in and severe is also more in also from corticosteroid therapy than In a study published earlier this year in Respirology, and colleagues the of gender on the in from in that but not were higher in of was also with higher levels of These some novel for the allergic response seen in published this year that this may also be controlled by One not investigated was the impact of age on this the prevalence of asthma is in prior to the onset of and were published this year in Respirology, one whether research have any impact on or treatment of respiratory and the whether is a therapeutic in the treatment of asthma. and the current such as and being in respiratory As the authors the to has been impact on therapeutic to it is not all and The of and with advances in and should several therapeutic in the and colleagues the current the impact of in asthma to whether this would be a for asthma an increased of have been seen in to airway and as such to airway of factors in several diseases has to whether the of these is a therapeutic to airway and several different including the immune response and the of it may be that by and will need to be to the impact of changes on asthma and of Children's Research of of of of of and and of for their to the is the Research in and a and work is in by the for