Fields of research

Early origins of lung diseases

The number of very premature babies who survive into childhood will continue to increase over the coming years and as a consequence, the number of children with chronic lung disease is also likely to increase. Pre-natal factors are known to influence lung health later in life and both nutritional deficiencies and maternal smoking have epigenetic influences on the developing lung. These epigenetic factors even seem to have transgenerational effects, which continue from grandmother to mother to daughter. Life expectancy for several congenital defects has also increased markedly with improved care, as infants with cystic fibrosis or neuromuscular disease benefit from early intervention with new targeted biological approaches.

Prevention of severe early infection is important, in order to reduce the incidence of life-threatening pneumonia or bronchiolitis, which can have consequences in adulthood in addition to their acute severe morbidity.

As well as impacting lung development, genetic and epigenetic factors related to the environment lead to alterations of defence mechanisms, with an undue inflammatory response to common allergens resulting in allergies in the form of rhinitis or asthma of varying severity, which often persist into adulthood. A more comprehensive understanding of these mechanisms is still needed in order to improve the treatments available.

Lifestyle and lung health

It has become increasingly apparent that lifestyle can impact lung health markedly. Nutritional deficiencies impair lung growth, favour infections and can decrease the ability to control inflammatory processes due, for instance, to a lack of antioxidative factors.

Lack of physical activity, often combined with obesity, impacts on disorders such as asthma or chronic obstructive pulmonary disease (COPD). Obesity also leads to obstructive sleep apnoea syndrome (OSAS), a condition whose prevalence has increased steadily over the past decade across all EU countries due to both better recognition of the disease and the increasing obesity of the population in general. The cardiovascular and metabolic consequences of OSAS are now recognised to be significant and will add to the overall burden of disease in Europe in the next decade.

Active and passive smoking are major factors in the aetiology of COPD and, of course, lung cancer. Asthma and COPD are the most prevalent respiratory diseases in the EU and the prevalence of both is increasing, placing a major burden on healthcare systems. There is a need to identify all contributory factors in these diseases, both intrinsic and extrinsic.

Sexual promiscuity and poverty have a major impact on the epidemiology of tuberculosis (TB), with an increase of its incidence particularly seen in the HIV-infected population. Respiratory infections in general are also frequent in such situations.

Drugs used to treat a variety of diseases can cause serious lung injury, resulting in pulmonary fibrosis or pulmonary hypertension, with possible fatal outcomes. Further research into these effects should help the relevant agencies develop prevention and management recommendations.

Lungs and the environment

The lungs are essentially wide open to the environment and have a very large surface area (approximately equal to that of a tennis court). Inspired air is separated from the blood in the pulmonary capillaries by a barrier of only about 1 μm. Inhaled particles of 2–10 μm in diameter are deposited in the airways and exposure to allergens and other particles contributes to asthma in 6–10% of the population, as well as to COPD, which is induced by exposure not only to smoking but also to indoor and outdoor pollution. The relevant indoor factors have still not all been identified. New volatile organic compounds used in construction and other industries have been added to better-known agents, such as sulfites, chlorates, isocyanates, and many other substances already known to be potentially toxic.

Asthma is an inflammatory disease of the airways secondary to known allergens and irritants, and several occupational agents have been shown to be responsible for its development. Some professions are well known to be at risk, such as bakers and carpenters; in other occupations, such as painting, building and hairdressing, asthma is induced by mechanisms that need to be further explored so that more effective preventive measures may be taken. Common cold viruses are also a very important trigger of asthma and, to reduce the ensuing morbidity, the mechanisms involved need to be better understood.

Carcinogens are abundant in tobacco smoke but other substances known to contribute to lung cancer originate in the environment. These include the radioactive element radon, which may be released naturally from the granite below houses, or asbestos extracted from mines and used for building insulation. Such compounds need to be identified and environmental exposure to them minimised. The mechanisms involved also need to be better understood in order to improve prevention and treatment.

As the climate changes during the coming century, environmental exposures are likely to alter, as atmospheric conditions and the distribution of flora and fauna change. This climate variation can to some extent be predicted and its impact on lung health needs to be further investigated.

Lung defences and infection

Acute lower respiratory tract infections (such as bacterial and viral pneumonia, influenza and respiratory syncytial virus infections) are the third most-frequent cause of death worldwide, accounting for 4.25 million deaths each year. The state of the lungs’ defences and the occurrence of infections are closely linked. A better understanding of how infections are prevented by the upper and lower airways is required; once we know how the defences function, we will have a clearer understanding of the way in which environmental factors and nutritional deficiencies may alter these defences to allow airway infections or pneumonia.

TB remains a leading cause of death worldwide, and any weakening of lung defences favours the occurrence of active disease and its propagation.

Where feasible, improvements in lung defences should be promoted – by the use of efficient vaccines, for example. The effects of immune-modulating agents, such as those used in treating malignancy and autoimmune diseases, need to be better understood in order to mitigate the effects of the resulting impairment of defences and the consequent severe secondary infections.

Early diagnosis of emerging new pathogens is crucial to allow appropriate use of new and existing therapies. New respiratory viruses appear quite frequently and rapid, reliable methods for diagnosis and typing of the viral strains need to be developed in the community. New vaccines and antiviral agents are also needed. Multidrug-resistant infectious agents and emerging fungal infections in immunocompromised patients are among other new challenges and new drugs against them need to be developed and tested.

Investigational technologies and imaging
Biological monitoring and biomarkers
New interventions and biological treatments
Table 2 – Fields where further biomedical research is needed.

Lung diseases in an ageing population

As European populations age, maintenance of good lung health will become a real challenge for current and future physicians. With age, both the upper and lower airways develop atrophic changes in the mucosa and thus the natural defences are altered. Elderly people tend to have more aspiration during swallowing and neuromuscular insufficiency may worsen their ability to cough. Humoral and cellular immunity also tend to alter with ageing. All these factors participate to varying degrees in the marked increase in lung infections that is seen with ageing, and the associated high morbidity and mortality. Physical activity, a comprehensive vaccination policy and good nutrition may help to prevent debilitating infections.

Ageing causes a reduction in the gas-exchange surface of the lungs, which may lead to a reduced capacity to oxygenate the blood. The airways become more collapsible, which contributes to obstructive lung disease. Prevention of undue inflammation related to environmental factors might decrease the effects of this natural decline in airway function.

Lung injury related to inhaled particles or to infections can produce scarring, sometimes leading to lung fibrosis and respiratory insufficiency. Some of these fibrotic processes may also be related to defects in natural repair and/or to a higher incidence of autoimmune diseases among older people. These immune processes lead not only to scarring of distal airways, but also in some patients to vascular narrowing and a higher incidence of pulmonary arterial hypertension with age.

The tissues of the body are continuously renewed by the division of progenitor cells. With ageing, dysregulation of these regeneration processes can occur, leading to various thoracic malignancies and tumours. Better knowledge of the effects of carcinogens should lead to improvement in effective prevention measures. Malignancy is also related to genetic factors and the identification of these may result in more individualised diagnostic screening and more personalised treatment.

See the entire Respiratory research Chapter