Epidemiological studies support the importance of adequate vitamin D status for the maintenance of pulmonary health and function; low levels of serum 25-hydroxyvitamin D 3 are associated with an increased incidence or poor control of asthma, respiratory infection and chronic obstructive pulmonary disease (COPD). 1–4 Vitamin D is proposed to support respiratory health through promoting antimicrobial functions necessary for efficient clearance of pathogens, and dampening inflammation with the potential to damage lung structure and impair gaseous exchange. 4 However, the role of its major carrier protein, vitamin D-binding protein (VDBP), is less well understood. A paper by Wood et al in Thorax 5 together with independent studies, highlight the potential of VDBP to influence respiratory function both by determining vitamin D bioavailability and via direct effects on innate cell function.
VDBP is a glycosylated α-globulin protein synthesised by many tissues including the liver, kidneys, gonads and fat, and also by neutrophils. It binds circulating 25(OH)-vitamin D and 1,25(OH) 2-vitamin D with high affinity. The levels of this protein far exceed circulating levels of these vitamin D metabolites, although VDBP has a rapid turnover rate. VDBP has three distinct domains which confer additional functions beyond carriage of vitamin D (reviewed by Chishimba et al 6). These functions include augmentation of the monocyte and neutrophil chemotactic response to the complement anaphylotoxin C5a, 7 8 scavenging of actin molecules released from necrotic cells 9 and, of interest to the current article, formation of a dimeric molecule with macrophage activating factor (DBP-MAF) which drives macrophages towards a more phagocytic phenotype with increased superoxide generation. 10 These activities of VDBP may be of particular …
In the spring of 2009 a novel influenza A virus (H1N1) of swine origin was identified in the USA and Mexico and rapid spread led to the declaration of a global influenza pandemic by the World Health Organization in June 2009. 1 2 The virus, which derives six genes from triple-reassortant North American swine virus lineages and two genes from Eurasian swine virus lineages, predominantly affected children and young adults with a low incidence of acute illness in those over 60 years of age. 3 By June 2010, cases had been identified in over 200 countries and territories worldwide and over 18 000 associated deaths were reported. 4
Infection with the pandemic virus caused a broad spectrum of clinical disease ranging from acute self-limiting upper respiratory tract illness with fever to fulminant pneumonitis and respiratory failure. Gastrointestinal and CNS symptoms were also common. Rates of admission to ICUs (13–45.3% of patients being hospitalised) were much higher than previously seen with seasonal influenza. 5–8 Rapid progression of severe hypoxaemia, typically starting on day 4–5 after the onset of symptoms, was observed with up to 80% of patients admitted to an ICU requiring mechanical ventilation. 6 Frequent radiological findings were of diffuse alveolar and interstitial infiltrates, often worse in the lower zones.
A number of risk factors were identified for the development of severe disease including age <2 years, pregnancy (highest risk in the third trimester), immunosuppression, morbid obesity, chronic cardiovascular and respiratory disease, diabetes and neuromuscular and neurocognitive conditions. The lowest rates of infection were seen in those aged >65 years, presumably relating to immunity conferred from prior exposure to antigenically-related H1N1 virus in previous outbreaks. Paradoxically, death …