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Provide brief responses to the questions below about the discussion readings. You can work in groups but you have to submit the assignment individually.
Wang 2018
1. Provide at least three reasons used by the authors to justify this study (from the Introduction).
2. What is the study design used to address the research question?
3. What is the purpose of the information presented in Table 1? What would you consider to be the main message(s) from that table?
4. Based on the results from this study, what do you consider to be the main risk factors for COPD in China? Why?
5. What are the main conclusions that can be derived from the information presented in Figure 3?
6. What are the main limitations of this study? Are they adequately discussed in the manuscript?
Rasmussen 2016
1.What is the main aim of the study presented in the article? What is the scientific rationale supporting this aim?
2.The authors conducted a nested case-control study. Why do you think they used this study design and not a cohort design?
3.What are the main findings from the study?
4.What is the purpose of Figure 3?
5.How did the authors evaluate the presence of unmeasured confounding?
6.What are the main strengths of the study?
7.What are the main limitations of the study?
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Series
Asthma 1
Risk factors for asthma: is prevention possible?
Richard Beasley, Alex Semprini, Edwin A Mitchell
Asthma is one of the most common diseases in the world, resulting in a substantial burden of disease. Although rates
of deaths due to asthma worldwide have reduced greatly over the past 25 years, no available therapeutic regimens can
cure asthma, and the burden of asthma will continue to be driven by increasing prevalence. The reasons for the
increase in asthma prevalence have not been defined, which limits the opportunities to develop targeted primary
prevention measures. Although associations are reported between a wide range of risk factors and childhood asthma,
substantiation of causality is inherently difficult from observational studies, and few risk factors have been assessed in
primary prevention studies. Furthermore, none of the primary prevention intervention strategies that have undergone
scrutiny in randomised controlled trials has provided sufficient evidence to lead to widespread implementation in
clinical practice. A better understanding of the factors that cause asthma is urgently needed, and this knowledge could
be used to develop public health and pharmacological primary prevention measures that are effective in reducing the
prevalence of asthma worldwide. To achieve this it will be necessary to think outside the box, not only in terms of risk
factors for the causation of asthma, but also the types of novel primary prevention strategies that are developed, and
the research methods used to provide the evidence base for their implementation. In the interim, public health efforts
should remain focused on measures with the potential to improve lung and general health, such as: reducing tobacco
smoking and environmental tobacco smoke exposure; reducing indoor and outdoor air pollution and occupational
exposures; reducing childhood obesity and encouraging a diet high in vegetables and fruit; improving feto-maternal
health; encouraging breastfeeding; promoting childhood vaccinations; and reducing social inequalities.
Introduction
Asthma is one of the most common chronic diseases in
the world, resulting in a substantial worldwide burden of
disease.1 The temporal trend of increasing prevalence of
asthma over the past 60 years (figure 1) is likely to
continue as transitional communities progressively
adopt lifestyles of high-income countries and become
urbanised.2 Over recent decades the public health priority
has been to improve the assessment and management of
asthma,3 resulting in a 42% reduction in age-standardised
asthma death rates worldwide between 1990 and 2013.4
However, as no therapeutic regimen can cure asthma,
such approaches will always have their limitations. As a
result, it is necessary to gain a better understanding of
the factors that cause asthma, and to develop alternative
public health and pharmacological primary preventive
measures that are effective in reducing the prevalence of
asthma worldwide. In this Series paper, we review
current evidence for the risk factors for asthma and its
primary prevention, and propose priorities for research
that will lead to the implementation of effective primary
intervention strategies.
Can asthma be prevented?
It is reasonable to suggest that asthma prevention is
possible,
because
standardised
international
epidemiological studies in both children and adults have
shown that some populations have very low asthma
symptom prevalence rates.5,6 These surveys have identified
worldwide patterns of asthma symptom prevalence that
are not accounted for by existing knowledge of the
causation of asthma,5,6 but they do provide data on risk
www.thelancet.com Vol 386 September 12, 2015
Lancet 2015; 386: 1075–85
See Editorial page 1014
This is the first in a Series of
two papers about Asthma
Medical Research Institute of
New Zealand, Wellington,
New Zealand
(Prof R Beasley DSc,
A Semprini MBBS); and
Department of Paediatrics,
Child and Youth Health,
University of Auckland,
Auckland New Zealand
(Prof E A Mitchell DSc)
Correspondence to:
Prof Richard Beasley, Medical
Research Institute of
New Zealand, Wellington 6242,
New Zealand
Richard.Beasley@mrinz.ac.nz
factors on which primary prevention measures might be
based. However, developing effective and feasible primary
prevention strategies has proven a difficult task because of
the range of potential risk factors, the inherent difficulty in
establishing causality from observational association
studies, the resources needed to undertake adequately
powered randomised controlled trials (RCTs) with
extended follow-up beyond infancy, and the scarcity and
often highly complex nature of primary prevention
intervention studies.
The heterogeneity and complex natural history of the
disease confound attempts to assess the importance of
individual risk factors or primary prevention strategies
that use single interventions. Asthma is a syndrome of
various overlapping phenotypes with defined clinical and
Search strategy and selection criteria
We searched PubMed using “Asthma” and “Primary
prevention”. We applied the filter for “clinical trial” and
reviewed the results to isolate primary prevention trial
reports. We searched Embase and World Health Organization
Clinical Trials Registry with the terms “asthma” and “primary
prevention” and reviewed the results for primary intervention
trials and duplicates from PubMed. We searched the Cochrane
Library database using the terms “Asthma” and “Primary
prevention” and applying “trials” filter. Further relevant
references were obtained from the reference lists of reviewed
manuscripts, including studies in which asthma was a
secondary outcome variable. Publications in all languages
and until March 17, 2015, were considered.
1075
Series
40
Australia
England and Wales
Scotland
Israel
Japan
New Zealand
Norway
Singapore
Sweden
Taiwan
USA
Netherlands
Italy
Greece
35
30
Prevalence (%)
25
20
15
10
5
0
1955
See Online for appendix
1960
1965
1970
1975
1980
Year
1985
1990
1995
2000
2005
Figure 1: Global trends in asthma symptom prevalence in children by country
Studies were selected in which at least two prevalence datapoints were obtained with the same asthma symptom criteria in the same age group, population and
geographical area. Countries were included if initial data available was from before 1985, to provide long-term international trends in asthma symptom prevalence.
Prevalence datapoints were a minimum of four years apart. The same diagnostic criteria were used in each study, although these were not standardised between
studies. The populations studied included children, ranging from 5 to 18 years. References for the studies included in this figure are provided in the appendix.
Example phenotypes
Age of onset
Childhood vs adult
Clinical
Episodic vs persistent
Pathophysiological
Partially reversible airflow obstruction
Comorbidities
Rhinosinusitis
Genetic
β2 receptor polymorphisms
Environmental risks
Occupational asthma
Inflammatory
Eosinophilic vs non-eosinophilic
Immunological
Atopic vs non-atopic
Biomarkers
Fractional exhaled nitric oxide
Endotypes
Aspirin sensitivity
Response to therapy
Steroid resistance
Severity
Amount of treatment needed to achieve control
Mortality risk
History of life threatening attack
Table 1: Examples of asthma phenotypes in relation to specific
characteristics
In this review we address the risk factors and primary
prevention strategies for childhood asthma, recognising
that most adult asthma first develops in childhood, and
that adult onset asthma often has its origins earlier in
life.8 We focus on school-age (5–18 years) rather than
preschool (younger than 5 years) children with asthma
because of the favourable natural history of transient
forms of wheezing during infancy.9 We do not
differentiate risk factors related to asthma severity,
recognising that measures to reduce risk of developing
asthma will lead to a disproportionately greater reduction
in the prevalence of severe asthma in the population.10
Risk factors are considered from the perspective of how
they might be relevant to the planning of primary
prevention intervention studies, from which public
health or pharmacological intervention strategies could
be developed.
Risk factors
physiological characteristics, underlying inflammatory
processes with identifiable biomarkers, genetic and
environmental risk factors (and their interactions),
response to therapies, natural history, and comorbidities.7
However, our understanding is insufficient to define
asthma phenotypes in this multidimensional, unifying
way, with approaches limited to the presence or absence
of individual characteristics, as outlined in table 1. It is
likely that there will be both common and different risk
factors across phenotypes, and that the opportunity exists
for both broad and narrowly targeted intervention
measures.
1076
A comprehensive list of risk factors for the development
of asthma in childhood is presented in table 2. Age is an
important consideration in respect of the different
phenotypes of childhood wheeze. Children with
persistent and late onset wheeze, but not those with
transient forms of wheezing up to 3 years of age, have
greater risk of having persistent childhood asthma.9
These findings suggest that for any primary prevention
strategy to target those at risk of persistent childhood
asthma, it would be necessary to identify early clinical,
immunological or genetic biomarkers for the chronic
forms of the disease.11 Sex affects the risk of asthma in an
www.thelancet.com Vol 386 September 12, 2015
Series
Association
Demographics, developmental, lifestyle
Association
(Continued from previous column)
Age
Nonlinear
Diet
Sex
Age dependent
Fruit and vegetables
Family history
Positive
Mediterranean diet
Negative
Genetics
Positive
Breastfeeding
Negative
Low gross national product
Negative
Raw milk
Negative
Agricultural subsistence
Negative
Probiotics
Negative
Urbanisation
Positive
Fast food
Positive
High-income lifestyle
Positive
Fish oils
Negative
High altitude
Negative
Selenium
Negative
Low birthweight or fast infant weight gain
Positive
Vitamin A
Negative
Preterm
Positive
Vitamin D
Negative
Caesarean delivery
Positive
Vitamin E
Negative
Atopic sensitisation
Positive
Magnesium
Negative
Rhinitis
Positive
Trans-fatty acids
Positive
Stress
Positive
Salt
Positive
Day care
Negative
Inhaled exposures
High body-mass index
Positive
Maternal smoking
Sedentary behaviour
Positive
Paternal smoking
Positive
Child smoking
Positive
Infection related
Negative
Positive
Respiratory syncytial virus
Positive
Indoor air pollution
Positive
Rhinovirus
Positive
Outdoor air pollution
Positive
Positive
Occupational exposure
Positive
Pertussis
Medication
House dust mite
Positive
Paracetamol
Positive
Endotoxin
Negative
β agonists
Positive
Farm animals
Negative
Antibiotics
Positive
Cats
Variable
(Table 2 continues in next column)
Moulds
Positive
age-dependent manner, with asthma being more
prevalent in boys until the age of 13 years, after which it
is more prevalent in girls.12 Understanding the complex
biological mechanisms that cause sex-associated
differences could guide preventive measures.12
Genetic predisposition is an important but poorly
characterised component of asthma risk. Family history
for asthma increases the risk to a child, however it is
clear that inheritance does not follow a straightforward
Mendelian pattern. Many loci across many chromosomes
have been associated with asthma,13 and inconsistency in
replicating linkages, methodological limitations, strong
chronological effect on gene expression, and the
heterogeneity of asthmatic phenotypes have frustrated
efforts to fully define the disease at the genetic level.14 A
better understanding of genetic and environmental
interactions will provide opportunities for novel targeted
treatments to reduce the risk of developing asthma and
its progression to severe disease.
The association between parental smoking and
childhood asthma risk now extends beyond maternal
smoking during pregnancy and throughout childhood to
a separate and additive association with paternal smoking
during childhood.15 Active smoking in childhood is an
important risk factor for asthma risk in adolescence.16
www.thelancet.com Vol 386 September 12, 2015
Variation exists in the strength and direction of associations, depending on
factors such as atopic versus non-atopic disease, population income, coexistence
of other risk factors, and methodological differences between studies. Categories
are broadly defined and individual risk factors may overlap.
Table 2: Reported associations between risk factors and childhood asthma
Real potential exists to reduce asthma risk through
reducing tobacco use.
Pre-term birth (
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