Global Burden of Chronic Respiratory Diseases

Abstract

Background:

Noncommunicable diseases (NCDs) and chronic respiratory diseases (CRDs) are the main causes of mortality and morbidity worldwide.

Methods:

The main evidences about the NCDs and CRDs burden and related risk factors, from updated international reports and results of original researches, were collected and described in this review.

Results:

Most recent evidence is available from the Global Burden of Diseases Study (GBD) 2017 reports. There were 3.2 million deaths due to chronic obstructive pulmonary disease (COPD) and 495,000 deaths due to asthma. COPD was the seventh leading cause of years of life lost (YLLs). Overall, prevalent cases of CRDs were 545 million: about 50% for COPD and 50% for asthma. Incident cases of CRDs were 62 million, mostly due to asthma (69%) and COPD (29%). COPD accounted for 81.6 million disability-adjusted life years, asthma for 22.8 million. COPD prevalence of 9.1% has been found in a recent general population sample of North-Eastern Italy, while in Central Italy a 25-year follow-up of a general population sample has shown an increased prevalence of COPD and asthma up to 6.8% and 7.8%, respectively. In Central Italy, a COPD incidence of 8% and an asthma incidence of 3.2% have been found in adult subjects at an 18-year follow-up. Among the risk factors, a relevant role is played by smoking and high body mass index for asthma, while smoking, particulate matter pollution, ambient ozone pollution, occupational exposure to particulate matter, gases and fumes, as well as second-hand smoke, play an important role for COPD. Forecasting the YLLs by 2040 indicates a rising toll from several NCDs due to population growth and aging, with COPD expected to reach the fourth leading cause.

Conclusions:

Several recent studies and international reports highlighted the huge global health burden of CRDs and other major NCDs, pointing out the need for implementing international collaborations to fight this epidemic trend.

Introduction

This review article summarizes the most recent information about mortality and morbidity of chronic respiratory diseases (CRDs), with a special focus on data from the Global Burden of Diseases Study (GBD) 2017.

GBD 2017 study includes 195 countries for which all-cause and cause-specific mortality were estimated, using the following key principles: identification of all available data sources; data quality assessment; correction for known bias; application of highly standardized analytical procedures; and assessment of model performance. Similar principles to identify, enhance comparability, and analyze data for estimating the incidence, prevalence, and years lived with disability (YLDs) of diseases and injuries were used.⁽¹⁾

Data used to estimate asthma and chronic obstructive pulmonary disease (COPD) mortality mainly included vital registration and surveillance data from the cause of death database, based on the International Classification of Diseases (ICD).⁽¹⁾

Data used to estimate asthma and COPD prevalence/incidence included hospitalization data, based on ICD codes, and epidemiological surveys data. For the latter, asthma was defined as a doctor's diagnosis and wheezing in the past year, while COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification.⁽²⁾ GBD 2017 included estimates for 2017, as well as it updated the entire series from 1980 used for GBD 2016. The list of included causes was expanded and study methods were improved in multiple ways.

For the other research articles included in this review, some methodological details are later on reported along with the studies' description.

Mortality

According to the results of the GBD Study 2017, noncommunicable diseases (NCDs) (i.e., diseases that are not directly transmissible from one person to another, such as cardiovascular diseases, respiratory diseases, cancer, neurological disorders) comprise the largest fraction of deaths, contributing to 73.4% of total deaths. Concerning respiratory diseases, there were 3.2 million deaths due to COPD and 495,000 deaths due to asthma.⁽¹⁾

The total number of deaths from NCDs increased by 22.7% from 2007 to 2017, representing an additional estimate of 7.61 million deaths (Fig. 1).⁽¹⁾ In particular, the number of deaths from CRDs increased globally by 15.8%: +17.5% for COPD and −0.7% for asthma.⁽¹⁾ COPD moved from the 11th to the 7th leading cause of years of life lost (YLLs) due to premature mortality, with a 13.2% increase.⁽¹⁾

FIG. 1.

GBD Study 2017. Percentage changes (and 95% confidence intervals) in mortality and morbidity indicators, 2007–2017. CRDs, chronic respiratory diseases; DALYs, disability-adjusted life years (i.e., the sum of years of potential life lost due to premature mortality and the years of productive life lost due to disability); GBD, Global Burden of Diseases Study; NCDs, noncommunicable diseases; YLDs, years lived with disability. Modified from Ref.⁽¹⁾

In Europe, 15% of deaths were estimated due to respiratory diseases,⁽³⁾ with 600,000 people dying every year.^(3,4) The 2015 age-standardized death rate for diseases of the respiratory system was 46.40 deaths per 100,000 individuals in Europe, of which 14.35 per 100,000 for chronic lower respiratory diseases.⁽⁵⁾

Morbidity

Globally, NCDs were the leading cause of disability-adjusted life years (DALYs) (i.e., the sum of years of potential life lost due to premature mortality and the years of productive life lost due to disability) for both men and women amounting to 1.6 billion in 2017. CRDs accounted for 112 million DALYs, of which 81.6 million were due to COPD and 22.8 million due to asthma.⁽⁶⁾ Within the GBD Study 2017, a 40.1% increase in DALYs due to NCDs emerged from 2007 to 2017, with a 14.5% increase due to CRDs (Fig. 1), particularly in females (18.9% vs. 10.7% in males). DALYs due to COPD increased by 21.2% in females and by 13.5% in males, whereas DALYs due to asthma showed a significant increase only in females (+9.7%).⁽⁶⁾

The all-age DALYs count of COPD rose from the 8th to the 6th leading cause from 2007 to 2017 in both genders; asthma remained stable in males (32nd cause) and rose from the 32nd to the 30th position in females.⁽⁶⁾

Furthermore, the European Respiratory Society (ERS) reported that 6 million hospital admissions were due to respiratory diseases in 2008,^(3,4) corresponding to 7% of total hospital admissions.⁽⁴⁾ In 2017, hospital in-patient admission rates (i.e., number of hospital admissions per 1000 inhabitants per year) for respiratory system diseases ranged from 6.20‰ in Iceland to 30.88‰ in Bulgaria: those for asthma ranged from 0.12‰ in Italy to 0.19‰ in Bulgaria and those for COPD and bronchiectasis ranged from 0.62‰ in Cyprus to 4.70‰ in Romania.⁽⁷⁾

Prevalence and Incidence

According to the GBD Study, in 2017, all-age prevalent cases of CRDs (i.e., individuals with CRDs in 2017) were 545 million, of which about 50% was due to COPD and about 50% due to asthma; all-age incident cases of CRDs (new cases of CRDs in 2017) were 62 million, mostly due to asthma (69%) and COPD (29%); all-age YLDs due to CRDs were 44 million (+22.8% from 2007 to 2017) (Fig. 1), mostly for COPD (69%) and asthma (24%).⁽²⁾

The leading causes of prevalence and YLDs were NCDs for both men and women. COPD remained stable as prevalence cause (20th rank) and decreased from the 8th to the 9th rank as YLDs cause in males from 2007 to 2017, while it moved from the 10th to the 6th rank as YLDs cause in females. Asthma moved from the 22nd to the 23rd rank as prevalence cause in males from 2007 to 2017; differently, it was not included among the first 30 leading causes of prevalence and YLDs in females.⁽²⁾

At European level, Eurostat data showed a prevalence (i.e., the ratio between the total number of cases of a disease and the total number of people studied at a specific time, usually expressed as a percentage) of 4.2% (4.0% in males and 4.3% in females) for chronic lower respiratory diseases (excluding asthma) in 2014, ranging from 1.2% in Malta to 7.7% in Turkey. A prevalence of 5.9% (5.2% in males and 6.6% in females) for asthma emerged in 2014, ranging from 2.0% in Romania to 9.8% in the United Kingdom.⁽⁷⁾

Some population-based studies investigated changes over a long time interval in the prevalence of respiratory symptoms and disorders using data reported by the investigated subjects through the use of standardized questionnaires (i.e., respiratory symptoms and physician-diagnosed diseases). A recent Italian study showed an increasing trend in prevalence rates of all investigated respiratory symptoms and diseases: in particular, current asthma attacks (from 3.4% to 7.2%) and COPD (from 2.1% to 6.8%) were more than doubled in a period of 25 years; asthma prevalence increased from 6.7% to 7.8%, even though not significantly.⁽⁸⁾ Indeed, such data are consistent with the Italian phase of the European Community Respiratory Health Survey (ECRHS), where an increase in the prevalence of current asthma (asthma symptoms in the last 12 months or current asthma medication) from 4.1% to 6.6% at a 20-year follow-up was found.⁽⁹⁾ A Swedish study showed a higher increase from 8.3% to 10% in the prevalence of asthma diagnosis at an 8-year follow-up of general population samples,⁽¹⁰⁾ while data from seven centers in North Europe found a mean increase of 4% in the prevalence of current asthma (asthma symptoms in the last 12 months or current asthma medication) at a 20-year follow-up.⁽¹¹⁾ As regards COPD, a GOLD-defined COPD adjusted prevalence increasing from 7% to 14% in 9 years was found in Norway.⁽¹²⁾ Conversely, the Italian ECRHS study showed a stable prevalence of chronic bronchitis (i.e., reported chronic cough or phlegm) (12.5%) in the period 1998–2010.⁽¹³⁾

With regard to new onsets of CRDs, one third of the population was estimated to develop asthma throughout life between the ages of 5 and 80 years, most before the age of 20 years.⁽³⁾ Some European studies showed a cumulative incidence (i.e., the ratio between the number of new cases of a disease within a specified time period and the size of the population initially at risk) of COPD diagnosis, defined according to spirometric criteria, ranging from 3% in young adults (20–44 years) to 7% in adults.^(14,15) Furthermore, incidence values of reported COPD diagnosis and of reported asthma diagnosis were 8% and 3.2% in adults at an 18-year follow-up, respectively.⁽¹⁶⁾

It is to point out that asthma may be an independent risk factor for COPD development. Indeed, a recent meta-analysis found that a prior history/diagnosis of asthma may increase the risk of COPD development later in life (odds ratio = 7.23; 95% confidence interval (CI) = 5.05–10.33).⁽¹⁷⁾ This result was supported by a study on lung function trajectories indicating that early childhood asthma was associated with accelerated decline and persistently poor lung function at 53 years of age, namely the two conditions that are more strictly linked to COPD occurrence.⁽¹⁸⁾

Future Projections

Based on the census bureau report, among the 7.3 billion people living worldwide in 2015, ∼8.5% are 65+ years. The number of elderly people is projected to increase by over 60% in just 15 years, reaching a value of 12.0% of the total population in 2030. This trend is expected to continue in the following 20 years, with 16.7% of the total world population represented by the elderly in 2050.⁽¹⁹⁾ Population aging is primarily due to lower fertility, but also reflects increased longevity. Today, living up to 70–80 years is no longer a rarity. Increasing longevity has led to new challenges: “How many years can older people expect to live in good health? What are the chronic diseases that they may have to deal with?.”⁽¹⁹⁾

It is well known that older people are typically more susceptible to chronic diseases, among which are respiratory diseases. Consequently, a further increase of such diseases is expected in the next years. Understanding the potential trajectories in health and health drivers is crucial to improve long-term investments and policies.⁽²⁰⁾

A recent article, based on the data from the GBD Study 2016, modeled life expectancy, all-cause mortality, and YLL forecasts for 250 causes of death, from 2016 to 2040, in 195 countries and territories.⁽²⁰⁾ A 4.4-year increase in global life expectancy was forecasted for both genders by 2040; 81.0% of global deaths and 67.3% of YLLs were forecasted to be due to NCDs.⁽²⁰⁾ The three leading causes of YLLs in 2040 are expected to remain the same as in 2016 (ischemic heart disease, stroke, and lower respiratory infections); on the contrary, most of the top 10 causes are expected to fall in rank. COPD is an exception, since it is expected to move from the ninth to the fourth rank worldwide (eighth rank in central Europe).⁽²⁰⁾

Considering the projected increase in the proportion of the world urban population (from 45% to 59% in 2025), it has been estimated that there may be 100 million more persons with asthma by 2025.⁽²¹⁾

In 2003, respiratory risk charts were developed in Italy to estimate individual absolute and relative risks of developing COPD in the subsequent 10 years, in relation to gender, age, smoking habit, occupational exposure, and environmental exposure⁽²²⁾: for example, a male smoker 55–64 years of age, with environmental and occupational exposures, has a >40% probability of developing COPD within the next 10 years; for a female with the same characteristics, the probability is 20–39%.

These results strengthen the need for early intervention on modifiable risk factors.⁽²²⁾

Risk Factors

Improvement of population health requires an understanding of the injuries and diseases responsible for health burdens, as well as a deep knowledge of their risk factors.⁽²³⁾

The previously described GBD 2016 study identified three metabolic risks (high blood pressure, high BMI, and high fasting plasma glucose) among the six leading global risk factors for premature mortality, along with tobacco, alcohol, and ambient air pollution.⁽²⁰⁾ Tobacco, air pollutants, occupational exposures, and climate changes are the main individual/environmental risk factors associated with lifetime increase of respiratory symptoms/diseases, according to the World Health Organization and several reviews.^(24–27)

With regard to climate changes, it is recognized that global warming increases the effects of outdoor air pollution on health: it leads to more heat waves, during which air pollution concentrations are also elevated and during which hot temperatures and air pollutants act in synergy to produce more serious health effects than expected from heat or pollution alone.⁽²⁸⁾

This concept has been reinforced by recent literature. A study carried out in Greater London reported a positive association between increasing temperatures and accident and emergency department attendances for cardiac, respiratory, cerebrovascular, and psychiatric conditions.⁽²⁹⁾ A Chinese study also showed that exposure to high temperatures increased emergency department visit risks from endocrine, respiratory, and digestive diseases and injury, with an overall attributable fraction due to high temperatures of 8.64%.⁽³⁰⁾

Climate change has a direct effect on temperature patterns and extreme weather events, as well as an indirect impact on public health through its influence on air quality.⁽³¹⁾ The European project APHEA2 had found a positive association between an increase in ozone concentration and an increase in the daily number of deaths (0.33%), in the number of respiratory deaths (1.13%), and in the number of cardiovascular deaths (0.45%) during the warm period of the year, while no effect had been observed during wintertime.⁽³²⁾ These results have also been confirmed by a Nationwide Multicounty Study in China.⁽³³⁾

Climate change, modifying the availability and distribution of plant- and fungal-derived allergens, influences the frequency and the severity of respiratory allergies increasing the effect of aeroallergens on the onset and aggravation of allergic respiratory diseases in sensitized and symptomatic patients, respectively.^(34,35) Thunderstorm-related asthma is a specific example of extreme climate event due to the occurrence of thunderstorms during the pollen season, inducing severe asthma attacks and deaths in pollen-allergic patients as happened during the pandemic thunderstorm-induced asthma of Melbourne in 2016, with the involvement of over 9000 persons and 10 deaths.⁽³⁵⁾

Thus, the reduction of factors causing air pollution and climate change may have relevant health cobenefits.⁽³⁶⁾ Indeed, a Spanish study found that the impact of weather changes differs greatly by pollutant, suggesting that the influence of weather changes may vary widely from transport phenomena such as advection or diffusion to atmospheric chemical reactions governing secondary pollutant formation. Furthermore, the study highlighted that PM₁₀ decrease has reduced the number of deaths attributable to air pollution over the 25-year study period by 33.047 (95% CI: −13,584 to 52,510). This benefit from air quality improvements in Spain would have been about 10% larger if weather conditions had not changed during the study period.⁽³¹⁾

The GBD 2017 study estimated levels and trends in exposure-attributable DALYs (i.e., DALYs due to risk factor exposure) and deaths for 84 behavioral, environmental, occupational, and metabolic risk factors from 1990 to 2017.⁽²³⁾ All risk-attributable DALYs for all causes declined by 4.9% and all risk-attributable deaths for all causes increased by 8.3% between 2007 and 2017; these values varied substantially according to the specific risk factor (Table 1) and specific disease. For example, an increase of attributable DALYs and deaths for COPD emerged: smoke-attributable DALYs increased by 7.8% and smoke-attributable deaths increased by 9.5%; particulate matter pollution-attributable DALYs and deaths increased by about 22–23%; ambient ozone pollution-attributable DALYs and deaths increased by 16.4% and 20.4%, respectively; occupational particulate matter, gas, and fume-attributable DALYs and deaths increased by 14.6% and 13.1%, respectively; second-hand smoke-attributable DALYs and deaths increased by 10.8% and 9.0%, respectively.⁽²³⁾ A decrease in smoke-attributable deaths (−15.5%) and an increase in high body mass index-attributable DALYs and deaths (27.0% and 23.9%, respectively) were estimated for asthma.⁽²³⁾

Table 1.

Global Burden of Diseases Study 2017. Percentage Change (95% Confidence Intervals) in Risk Factor-Attributable Deaths and DALYs Due to All Causes, 2007–2017.

	Percentage change in deaths	Percentage change in DALYs
All risk factors	8.3% (6.9%–9.5%)	−4.9% (−6.5% to −3.3%)
Environmental and occupational risks	2.2% (−0.3% to 4.7%)	−10.7% (−13.7% to −7.5%)
Air pollution	5.8% (3.0%–8.8%)	−6.6% (−9.8% to −2.8%)
Ambient particulate matter pollution	21.6% (16.2%–26.8%)	12.8% (5.6%–20.2%)
Household air pollution from solid fuels	−16.3% (−20.2% to −11.9%)	−25.8% (−30.2% to −20.9%)
Ambient ozone pollution	20.4% (15.9%–24.5%)	16.4% (12.0%–20.6%)
Occupational risks	6.5% (3.5%–9.4%)	6.7% (4.1%–9.3%)
Smoking	11.2% (8.8%–13.5%)	8.2% (6.0%–10.3%)
Alcohol use	11.0% (3.2%–19.1%)	5.5% (0.5%–10.7%)

Modified by Ref.⁽²³⁾

DALYs, disability-adjusted life years.

The risk of increasing DALYs due to smoking and ambient particulate matter increased between 2007 and 2017 (from the 3rd to the 2nd rank and from the 13th to the 10th rank, respectively); a decrease emerged for the risk due to household air pollution (from the 12th to the 16th rank).⁽²³⁾

GBD authors also computed temporal changes in the absolute number of DALYs as a result of changes in six underlying components: population growth, population aging, environmental/occupational risk, behavioral risk, metabolic risk, and all other factors (risk-deleted or residual). In particular, the decrease of exposure to environmental/occupational risks would have determined a 2.6% decline in DALYs from all causes for both genders, with a decline of about 6% for NCDs⁽²³⁾; this is the only risk category that was a driver of decline for all the cause groups and both sexes.

The European Environment Agency estimated that in the EU-28 a total of 13–19% of the urban population was exposed to PM₁₀ levels above the EU daily limit value, whereas 42–52% was exposed to concentrations exceeding the World Health Organization (WHO) Air Quality Guidelines (AQG)’ value for PM₁₀. Concerning PM_2.5, 6–8% of the urban population was exposed to levels above the EU limit value, while 74–85% was exposed to concentrations exceeding the WHO AQG. 7–8% of the population was exposed to levels above EU and WHO values for NO_2, while 7–30% was exposed to levels above the EU limit value and ∼100% above the WHO AQG values for O₃.⁽³⁷⁾ In addition, in the same report, the premature deaths and YLLs in the EU-28 due to air pollutants' exposure in 2015 were analyzed: 391,000 premature deaths and 4.15 million YLLs were attributed to PM_2.5 exposure; 76,000 premature deaths and 795,000 YLLs were attributed to NO₂; 16,400 premature deaths and 180,000 YLLs were attributed to O₃ exposure.⁽³⁷⁾

Substantial reduction of NCDs mortality requires policies aimed to reduce tobacco and alcohol use, blood pressure, and environmental risk factors, as well as to obtain fair access to effective and high-quality preventive care for NCDs.⁽³⁸⁾ Indeed, in 2016, an estimated 4% of NCDs deaths occurred in people younger than 30 years of age, 38% in people 30 to 70 years of age, and 58% in people 70+ years of age. Women in 88% and men in 89% of 186 countries and territories had a higher probability of dying before 70 years of age from an NCD than from communicable, maternal, perinatal, and nutritional conditions combined. Globally, the lowest risks of NCDs mortality in 2016 were seen in high-income countries.

Sustainable Development Goal (SDG) target 3.4 (i.e., one-third reduction, relative to 2015 levels, in the probability of dying between 30 and 70 years of age from NCDs by 2030) will be achieved in 19% of countries for women, and 16% of countries for men, if these countries will maintain or surpass their 2010–2016 rate of decline in NCD mortality.⁽³⁸⁾

A quantitative assessment of the effect on longevity after meeting the SDG target of 3.4 is one of the important measures needed to advocate and inform national disease control policies.⁽³⁹⁾

Recently, a global analysis to estimate improvements in average expected years lived between 30 and 70 years of age that would result from meeting the SDG target was performed. A one-third reduction in premature mortality from the major NCDs in 2015–2030 would have substantial effects on national longevity. In fact, between 30 and 70 years of age, worldwide average gains in life years lived of 0.80 years for all NCDs and 0.64 years for the four major NCDs (cardiovascular diseases, cancer, CRDs, and diabetes) are expected from reduced premature mortality. In high-income countries, the same estimated values are 0.52 years for all NCDs and 0.40 years for the four major NCDs.⁽³⁹⁾ In particular, a 0.09-year average gain in life years lived is expected for CRDs worldwide (0.05 years in high-income countries).⁽³⁹⁾ Furthermore, if all CRDs deaths in people 30–70 years of age were removed, the average gain in life years lived would be 0.17 years worldwide and 0.09 years in high-income countries.⁽³⁹⁾

In light of these results, intervening on modifiable risk factors today will give the opportunity to reduce avoidable mortality in the future.⁽²⁰⁾

Economic Impact

Beside mortality and morbidity, costs indicate the burden due to a specific disease on society.

The economic burden of CRDs is substantial. According to the European Lung White Book, the European COPD annual direct costs (health care) were 23.3 billion Euros, while the indirect costs (lost production) were 25.1 billion in the year 2011; the same figures for asthma were 19.5 billion and 14.4 billion Euros, respectively.⁽⁴⁾ The annual costs per case were €2100 for COPD and €3400 for asthma. Indirect costs accounted for 52% and 43% of COPD- and asthma-related costs, respectively.⁽⁴⁾

A recent review of worldwide studies showed that annual costs per person/year (py) varied from less than US$150/py to more than US$3000/py and those for COPD varied from US$536/py to US$4528/py.⁽⁴⁰⁾ This wide range may be ascribed to different methodologies (inclusion criteria, data sources, and disease severity) used in the cost-of-illness studies.

This aspect makes it difficult to associate differences in reported costs with differences in the true burden of asthma and COPD. However, despite the large variability, these data highlight how CRDs continue to determine a major economic burden across many countries.⁽⁴⁰⁾

Conclusions

Several recent studies and international reports estimated the huge global health burden of CRDs and other major NCDs, pointing out the need for implementing international collaborations to fight this epidemic trend.

The Global Alliance Against Chronic Respiratory Diseases (GARD) is an alliance of WHO and national and international organizations, medical and scientific societies, institutions and agencies, all working with the common goal of reducing the global burden of CRDs. The concept of GARD is a world where all people breathe freely. To achieve this goal, GARD has defined four strategic objectives:⁽⁴¹⁾

(I)

Advocacy. To raise the recognition of the importance of CRDs at global and country levels, and to advocate the integration of the prevention and control of such diseases into policies across all government departments;

I) Partnership. To promote partnering for the prevention and control of CRDs;

II) National plans on prevention and control. To support WHO in assisting countries to establish and strengthen national policies and plans for the prevention and control of CRDs using WHO-endorsed approaches and methods;

V) Surveillance. To support WHO in monitoring CRDs and their determinants and to evaluate progress at country, regional, and global levels.

Footnotes

Author Disclosure Statement

The authors declare they have no competing financial interests.

Funding Information

This work was supported in part by the National Institute for the Insurance of Occupational Injuries (INAIL) in the framework of the Call on Research and Collaboration 2016–2018 (project No 04/2016: BEEP).

Reviewed by:

Mark Utell

Federico Lavorini

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