Nutritional Requirements of the Respiratory System - KORE Fit Living
How to Boost the Immune System in Teenagers. Furthermore, results from a large well designed RCT in adults with asthma showed no positive benefit of selenium supplementation [ ]. Inhibition of vitamin D receptor translocation by cigarette smoking extracts. Airway inflammation is augmented by obesity and fatty acids in asthma. A small study in Sweden found that in older subjects with severe COPD, intakes of folic acid and selenium were below recommended levels, and although intake of calcium was adequate, serum calcium levels were low, likely related to their vitamin D status as intake was lower than recommended [ ]. It is possible that COPD onset may also be impacted by cellular responses to cigarette smoke exposure which inhibits the protective immunomodulatory effects of vitamin D [ ]. Studies on dietary intake of minerals and associations with COPD are sparse.
A variety of diseases can affect the respiratory system, such as asthma, emphysema, chronic obstructive pulmonary disorder COPD , and lung cancer. All of these conditions affect the gas exchange process and result in labored breathing and other difficulties. The major organs of the respiratory system function primarily to provide oxygen to body tissues for cellular respiration, remove the waste product carbon dioxide, and help to maintain acid-base balance. Portions of the respiratory system are also used for non-vital functions, such as sensing odors, producing speech, and for straining, such as during childbirth or coughing.
The major respiratory structures span the nasal cavity to the diaphragm. Functionally, the respiratory system can be divided into a conducting zone and a respiratory zone.
The conducting zone of the respiratory system includes the organs and structures not directly involved in gas exchange trachea and bronchi. The gas exchange occurs in the respiratory zone.
The major functions of the conducting zone are to provide a route for incoming and outgoing air, remove debris and pathogens from the incoming air, and warm and humidify the incoming air. Several structures within the conducting zone perform other functions as well.
The epithelium of the nasal passages, for example, is essential to sensing odors, and the bronchial epithelium that lines the lungs can metabolize some airborne carcinogens. The conducting zone includes the nose and its adjacent structures, the pharynx, the larynx, the trachea, and the bronchi. In contrast to the conducting zone, the respiratory zone includes structures that are directly involved in gas exchange.
The respiratory zone begins where the terminal bronchioles join a respiratory bronchiole, the smallest type of bronchiole Figure 2. Women and children breathe at a faster rate than men. The surface area of the lungs is roughly the same size as a tennis court! If all the alveoli in both lungs were flattened out, they would have a total area of about square feet! We lose about 12 oz of water of water a day through breathing.
In addition to exhaling carbon dioxide, you also exhale water. Lungs are the only human organ that can float in water! Each of your lungs contains about million balloon-like structures called alveoli, which replace the carbon-dioxide waste in your blood with oxygen.
Similarly in adults, the data is heterogeneous, with omega-3 PUFAs or fish being associated with improved lung function [ 38 ] and decreased risk of asthma [ 39 ], AHR [ 35 ] and wheeze [ 36 ] in some, but not all studies [ 40 ]. Maternal dietary intake of oily fish was found to be protective of asthma in children 5 years of age if born to mothers with asthma [ 41 ] and a recent systematic review of omega-3 fatty acid supplementation studies in women during pregnancy found that the risk of asthma development in children was reduced [ 42 ].
The data examining the possible benefits of dietary omega-3 fatty acid supplementation in asthma are heterogeneous and as summarized by a Cochrane review [ 43 ], to date there is insufficient evidence to recommend omega-3 PUFA supplementation in asthma.
Several studies using omega-3 PUFA supplementation in COPD are currently underway and will provide important new information to inform the field [ 47 , 48 , 49 ].
Dietary antioxidants are an important dietary factor in protecting against the damaging effects of oxidative stress in the airways, a characteristic of respiratory diseases [ 50 ]. Oxidative stress caused by reactive oxygen species ROS , is generated in the lungs due to various exposures, such as air pollution, airborne irritants and typical airway inflammatory cell responses [ 51 ].
Antioxidants including vitamin C, vitamin E, flavonoids and carotenoids are abundantly present in fruits and vegetables, as well as nuts, vegetable oils, cocoa, red wine and green tea. Dietary antioxidants may have beneficial effects on respiratory health, from influences of the maternal diet on the fetus, and intake in children through to adults and pregnant women with asthma and adults with COPD. This group of fat soluble antioxidants have been shown to benefit respiratory health due to their ability to scavenge ROS and reduce oxidative stress [ 22 ].
The antioxidant lycopene, present predominantly in tomatoes, may be beneficial in respiratory conditions, indeed lycopene intake has been positively correlated with FEV 1 in both asthma and COPD [ 53 ] and an intervention study in asthma showed that lycopene supplementation could suppress neutrophilic airway inflammation [ 54 ]. Antioxidants may also be important in asthma during pregnancy, as while oxidative stress commonly increases during normal pregnancies, in women with asthma oxidative stress is heightened [ 55 ].
During pregnancy there is a compensatory increase in circulating and placental antioxidants in asthma versus women without asthma, to protect the foetus against damaging effects of oxidative stress [ 55 , 56 ]. Improving antioxidant intake in pregnant women with asthma may be beneficial as poor fetal growth outcomes are associated with low levels of circulating antioxidants and dietary antioxidants are the first defense mechanism against ROS [ 22 ].
Maternal intake of vitamin E, vitamin D, milk, cheese and calcium during pregnancy are negatively associated, while vitamin C is positively associated, with wheezing in early childhood [ 57 , 58 ]. Antioxidants including lycopene appear to have positive influences in respiratory conditions, further detail is provided below on evidence for vitamin C, vitamin E and flavonoids and their role in the maternal diet, diets of children and adults with asthma and adults with COPD.
Vitamin C has been enthusiastically investigated for benefits in asthma and links to asthma prevention.
Anti-inflammatory and anti-asthmatic effects of vitamin C supplementation in vivo , have been shown through allergic mouse models of asthma. While Chang et al. Observational studies in children showed consumption of fruit, a rich source of vitamin C, was related to reduced wheezing [ 62 ] and vitamin C intake was negatively associated with wheezing [ 63 ], while another study reported no relationship between vitamin C intake and lung function [ 64 ].
Despite the observational data linking vitamin C to lung health, supplementation with vitamin C has not been shown to reduce the risk of asthma [ 66 ] which may be related to the interdependence of nutrients found in foods, resulting in lack of efficacy when supplementing with isolated nutrients. Evidence from experimental and observational studies suggests that Vitamin C might be important in COPD pathogenesis and management. A case control study in Taiwan reported that subjects with COPD had lower dietary intake and lower serum levels of vitamin C than healthy controls [ 68 ].
Indeed an epidemiological study in the United Kingdom of over adults aged 45—74 years found that increased plasma vitamin C concentration was associated with a decreased risk of obstructive airways disease, suggestive of a protective effect [ 69 ]. Thus, in summary, while observational data has suggested that vitamin C is important for lung health, intervention trials showing efficacy are lacking and it appears that supplementation with vitamin C-rich whole foods, such as fruit and vegetables may be more effective.
Vitamin E works synergistically with vitamin C, as following neutralisation of ROS, oxidised vitamin E isoforms can be processed back into their reduced form by vitamin C [ 71 ].
In COPD, serum levels of vitamin E have been shown to be decreased during exacerbation, which suggests increased intake may be helpful to improve vitamin E concentrations [ 84 ]. The offspring also showed reduced development of lung dendritic cells, necessary for producing allergic responses.
Evidence from observational studies also suggests that reduced maternal dietary intake of vitamin E is related to an increased risk of childhood asthma and wheeze [ 90 , 91 , 92 ] and increased in vitro proliferative responses in cord blood mononuclear cells CBMC [ 93 ]. A mechanistic study by Wassall et al. This study by Wassall et al. In asthma the experimental data for vitamin E are compelling, yet supplementation benefits are not well described.
Flavonoids are potent antioxidants and have anti-inflammatory as well as anti-allergic actions due in part, to their ability to neutralise ROS [ 95 ]. There are 6 classes of flavonoids including flavones, flavonols, flavanones, isoflavones and flavanols [ 96 ], which are widely distributed throughout the diet and found in fruit, vegetables, nuts, seeds, stems, flowers, roots, bark, dark chocolate, tea, wine and coffee [ 96 ].
Experimental studies of flavonoids in animal models of allergic asthma have shown reduced airway and peripheral blood inflammation, decreased bronchoconstriction and AHR and lower eosinophils in BALF, blood and lung tissue [ , , , ]. In humans, evidence from a case control study in adults showed that apple and red wine consumption, rich sources of flavonoids, was associated with reduced asthma prevalence and severity [ 66 ]. However a follow-up study investigating intake of 3 subclasses of flavonoids did not find any associations with asthma prevalence or severity [ ].
There are a limited number of experimental studies using flavonoid supplements in humans with asthma. There is a paucity of evidence for the effects of flavonoids in the maternal diet and respiratory outcomes in children. One study which found a positive association of maternal apple intake and asthma in children at 5 years, suggests that the flavonoid content of apples may be responsible for the beneficial relationship [ ].
Evidence for the effects of flavonoids in respiratory conditions is emerging and promising. Though like vitamin C, it may be difficult to disentangle the effects of flavonoids from other nutrients in flavonoid-rich foods.
Supplementation of individual flavonoids in experimental animal studies has provided evidence to suggest that intervention trials in humans may be warranted. Epidemiological studies show promising associations between vitamin D and lung health; however the mechanisms responsible for these effects are poorly understood.
Vitamin D can be obtained from dietary sources or supplementation; however sun exposure is the main contributor to vitamin D levels [ ]. While vitamin D has beneficial effects independent of UV exposure [ ], it can be difficult to separate this potential confounder from direct effects of vitamin D on lung health [ ]. The review by Foong and Zosky [ ] presents the current evidence for the role of vitamin D deficiency in disease onset, progression and exacerbation in respiratory infections, asthma and COPD.
Respiratory infections contribute to disease progression and exacerbation in both COPD and asthma. Vitamin D appears to have a protective role against the susceptibility to and severity of these infections [ ], as active vitamin D 1,25 OH 2 D modifies production of antimicrobial cathelicidins and defensins that kill bacteria and induce wound repair [ ]. In vitro studies also support the link between vitamin D and airway remodelling as active vitamin D inhibits airway smooth muscle ASM cell proliferation [ ] and deficiency impairs normal lung development [ ].
Furthermore, animal models suggest that vitamin D can inhibit Th1 and Th2 cell cytokine production [ ]. Epidemiological evidence links low levels of vitamin D with wheeze and respiratory infections, though evidence for the link with asthma onset is weak and inconsistent [ ].
In children, low circulating vitamin D was related to lower lung function, increased corticosteroid use and exacerbation frequency [ ]. Also in children with steroid resistant asthma, low vitamin D was related to increased ASM thickness [ ]. Other observational studies report that in children, low levels of vitamin D are associated with asthma exacerbation [ ].
Several observational studies support the role of vitamin D for protection against respiratory conditions in children. The role for vitamin D in enhancing steroid responsiveness suggested by observational studies [ ] is supported by mechanistic studies [ ], and in concert with the actions of vitamin D in infection, may explain the effect of vitamin D in reducing asthma exacerbations [ ]. Only one intervention trial has been conducted using vitamin D in adults with asthma, which found that rate of first exacerbation was reduced in subjects who demonstrated an increase in circulating vitamin D3 following supplementation [ ].
Data for the role of vitamin D in COPD onset is limited, though several cross-sectional studies have reported an association between low vitamin D levels, or deficiency, with COPD incidence [ ]. Experimental data suggest that vitamin D may be important in COPD for its effect on normal lung growth and development, though human data to support this is not available.
It is possible that COPD onset may also be impacted by cellular responses to cigarette smoke exposure which inhibits the protective immunomodulatory effects of vitamin D [ ].
COPD progression may also be affected by vitamin D status through absence of the vitamin D receptor and parenchyma degradation [ ]. COPD exacerbations are generally caused by viral or bacterial lung infections, and though vitamin D has a positive role in reducing infection, there is no evidence to support that vitamin D is associated with ameliorating exacerbations in COPD patients [ ]. The extra-skeletal effects of vitamin D are well documented in both asthma and COPD, and deficiency is associated with negative respiratory and immune outcomes.
Some minerals have also been found to be protective in respiratory conditions. In children, increased intake of magnesium, calcium and potassium is inversely related to asthma prevalence [ 7 ]. While several observational and experimental trials have been performed with conflicting results [ ], a randomised controlled trial concluded that a low sodium diet had no therapeutic benefit for bronchial reactivity in adults with asthma [ ].
Dietary magnesium may have beneficial bronchodilator effects in asthma [ ]. Low dietary magnesium intake has been associated with negative effects on bronchial smooth muscle in severe asthma [ ] and with lower lung function in children [ ]. However further evidence of positive therapeutic effects are required before its importance in asthma and recommendations can be determined [ ].
Dietary intake of selenium has been shown to be lower in asthmatics compared to non-asthmatics [ ] and maternal plasma selenium levels were reported to be inversely associated with risk of asthma in children [ ]. However case control studies in children have not found a relationship with selenium levels or intake with asthma related outcomes [ 18 , ]. Furthermore, results from a large well designed RCT in adults with asthma showed no positive benefit of selenium supplementation [ ].
Investigation of minerals in cord blood imply the importance of adequate intake during pregnancy, as levels of cord blood selenium were negatively associated with persistent wheeze, and levels of iron were negatively associated with later onset wheeze in children [ ]. Studies on dietary intake of minerals and associations with COPD are sparse.
A small study in Sweden found that in older subjects with severe COPD, intakes of folic acid and selenium were below recommended levels, and although intake of calcium was adequate, serum calcium levels were low, likely related to their vitamin D status as intake was lower than recommended [ ]. Mineral intake may be important in respiratory diseases, yet evidence for supplementation is weak. It is likely that adequate intake of these nutrients in a whole diet approach is sufficient.
Overnutrition and resulting obesity are clearly linked with asthma, though the mechanisms involved are still under investigation. The review by Periyalil et al. In the obese state dietary intake of lipids leads to increased circulating free fatty acids [ ], which activate immune responses, such as activation of TLR4, leading to increased inflammation, both systemically and in the airways [ 20 ].
Adipose tissue also secretes adipokines and asthmatic subjects have higher concentrations of circulating leptin than healthy controls [ 14 ] which are further increased in females, though leptin is associated with BMI in both males and females [ ]. Leptin receptors are present in the bronchial and alveolar epithelial cells and leptin has been shown to induce activation of alveolar macrophages [ ] and have indirect effects on neutrophils [ ].
In vitro , leptin also activates alveolar macrophages taken from obese asthmatics, which induces airway inflammation through production of pro-inflammatory cytokines [ ]. However, a causal role for leptin in the obese asthma relationship is yet to be established. Adiponectin, an anti-inflammatory adipokine, has beneficial effects in animal models of asthma [ ], however, positive associations in human studies have only been seen in women [ ].
In obesity, macrophage and mast cell infiltration into adipose tissue is upregulated [ ]. Neutrophils also appear to dominate airway inflammation in the obese asthma phenotype [ ], particularly in females [ ], which may explain why inhaled corticosteroids are less effective in achieving control in obese asthma [ ]. While the mechanisms are yet to be understood, a recent review reports that obesity in pregnancy is associated with higher odds of asthma in children, with increased risk as maternal BMI increases [ ].
COPD is characterised not only by pulmonary deficits but also by chronic systemic inflammation and co-morbidities which may develop in response to the metabolic dysregulation that occurs with excess adipose tissue [ ].
A recent meta-analysis of leptin levels in COPD reported a correlation with body mass index BMI and fat mass percent in stable COPD though absolute levels were not different to healthy controls [ ]. Adiponectin has anti-inflammatory effects and is present in high concentrations in serum of healthy subjects [ ]. Adiponectin exists in several isoforms, which have varied biological effects [ ] and interact with two receptors present in the lungs AdipoR1 and AdipoR2 that have opposing effects on inflammation [ ].
Single nucleotide polymorphisms in the gene encoding adiponectin are associated with cardiovascular disease, obesity and the metabolic syndrome [ ]. The role of adiponectin in COPD however is not well understood. In COPD, serum adiponectin is increased and directly relates to disease severity and lung function decline [ ].
There is an alteration in the oligomerisation of adiponectin in COPD resulting in increased concentrations of the anti-inflammatory higher-molecular weight isoform [ ], and the expression of adiponectin receptors in the lung is also altered in comparison to healthy subjects [ ]. However under certain conditions in cell lines and animal models adiponectin has been shown to have pro-inflammatory effects [ , ].
As both detrimental and protective effects have been seen, the complex modulation of adiponectin isoforms and receptors in COPD requires further exploration.
Obesity, the resulting systemic inflammation and alterations in adipokines have significant negative effects in both asthma and COPD. While work examining the mechanisms of effect is extensive, evidence for interventions to improve the course of disease are limited to weight loss interventions in asthma at this stage.
Though underweight has not been well studied in asthma, an observational study in Japan reported that subjects with asthma who were underweight had poorer asthma control than their normal weight counterparts [ ]. While there is widespread acknowledgement that malnutrition in pregnant women adversely effects of the lung development of the fetus [ ], a recent review reported that the offspring of mothers who were underweight did not have an increased risk of asthma.
Amongst the obstructive lung diseases, undernutrition is most commonly recognised as a feature of COPD. Weight loss, low body weight and muscle wasting are common in COPD patients with advanced disease and are associated with reduced survival time and an increased risk of exacerbation [ ].
The causes of undernutrition in COPD are multifactorial and include reduced energy intake due to decreased appetite, depression, lower physical activity and dyspnoea while eating [ ]. In addition, resting energy expenditure is increased in COPD, likely due to higher energy demands from increased work of breathing [ ]. Also, systemic inflammation which is a hallmark of COPD, may influence energy intake and expenditure [ ]. Cigarette smoke may also have deleterious effects on body composition in addition to the systemic effects of COPD.
Smoking causes muscle fibre atrophy and decreased muscle oxidative capacity shown in cohorts of non-COPD smokers [ , ] and in animal models of chronic smoke exposure [ , ]. The mechanisms underlying muscle wasting in COPD are complex and multifaceted [ ].
Increased protein degradation occurs in the whole body, though it is enhanced in the diaphragm [ ]. Protein synthesis pathways are altered, indeed insulin like growth factor-1 IGF-1 which is essential for muscle synthesis is decreased in cachectic COPD patients [ ] and is lower in COPD patients during acute exacerbation, compared to healthy controls [ ].
Furthermore myostatin induces muscle atrophy by inhibiting proliferation of myoblasts and mRNA expression of myostain is increased in cachectic COPD patients and is related to muscle mass [ ]. Nutritional supplementation therapy in undernourished COPD patients has been shown to induce weight gain, increase fat free mass, increase grip strength and exercise tolerance as well as improve quality of life [ ].
Further studies point out the importance of not only high energy content, but also macronutrient composition of the nutritional supplement and inclusion of low intensity respiratory rehabilitation exercise [ , ]. Other dietary nutrients have been investigated for the benefits in COPD. Creatinine, found in meat and fish, did not have additive effects to rehabilitation, while sulforaphane, found in broccoli and wasabi, and curcumin, the pigment in turmeric, may have beneficial antioxidant properties [ , , ].
Branched chain amino acid supplementation in COPD is associated with positive results including increases in whole body protein synthesis, body weight, fat free mass and arterial blood oxygen levels [ , ].
Undernutrition is not a significant problem in asthma, though is a major debilitating feature of COPD. There is promising evidence that nutritional supplementation in COPD is important and can help to alleviate some of the adverse effects of the disease, particularly muscle wasting and weight loss. Dietary intake appears to be important in both the development and management of respiratory diseases, shown through epidemiological and cross-sectional studies and supported by mechanistic studies in animal models.
Although more evidence is needed from intervention studies in humans, there is a clear link for some nutrients and dietary patterns. The dietary patterns associated with benefits in respiratory diseases include high fruit and vegetable intake, Mediterranean style diet, fish and omega-3 intake, while fast food intake and westernised dietary patterns have adverse associations.
Figure 1 shows a diagrammatic representation of the relationships of nutrition and obstructive lung diseases. Relationship of Nutrition and Obstructive Lung Diseases: Dietary factors that have been linked to respiratory disease.
Though antioxidants are associated with positive effects on inflammation, clinical outcomes and respiratory disease prevention, intervention studies of individual antioxidants do not indicate widespread adoption of supplementation [ ].