The Spanish influenza pandemic seen through the BMJ’s eyes: observations and unanswered questionsBMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b5313 (Published 16 December 2009) Cite this as: BMJ 2009;339:b5313
All rapid responses
Apparently there is an "urban myth" in China that students going to
study in the UK will suffer no real respiratory illness for at least 6
months after arrival. This is thought to be due to the pollutants in their
lungs being too much for the pathogens. After 6 months, their lungs are
becoming reasonably clean, and illness may result.
The idea that respiratory illness might be virtually unknown in the
early part of a stay was initially counter-intuitive - I might have
expected the reverse, with sudden exposure to a different pathogen
So, another possible mechanism, and a possible study population ?
Competing interests: No competing interests
The protection from the Spanish influenza pandemic cordite workers
(30.1% vs 4.7%)and tin workers (60.8% vs 11.1%) appear to have received
from exposure to toxic fumes reported in this review of old BMJ papers is
most interesting. From the comments quoted from Ball, Shufflebottom and
Gregor's observations, published in the BMJ in 1919 and 1920, consumption
was "practically unknown" in copper workers exposed to SO2, poison gas
workers exposed to sulphur acids and other workers exposed to NO2, SO2 and
mustard gas, which is a sulphur mustard, expsoure to the acidic products
of SO2 and NO2 might have been responsible for the immunity apparently
conferred by exposure to toxic fumes. Exposure to phosgene, COCl2,
appeared to have the opposite effect but the poison gas workers were also
exposed to chlorine products and they were "practically immune from
influenza". If this protection was real how might it have been induced? By
"Non-lethal ischemia of internal organs induces local (ischemic
preconditioning) and systemic (RIPC [remote ischaemic preconditioning])
resistance to lethal ischemia-reperfusion (IR) injury... Experimental RIPC
has two temporal components, is neuronally mediated, is induced by limb
ischemia, and reduces infarct size. In humans, RIPC prevents IR-induced
vascular injury. Remote ischemic preconditioning in humans has two phases
of protection against endothelial IR injury; an early (short) and late
(prolonged) phase, both of which are neuronally mediated" (1). In rat
heart, "ISF [interstitial fluid]ATP and adenosine increased temporarily by
10-fold during IPC [ischaemic preconditioning]. AMP-CP augmented the
increase in ISF ATP associated with the decrease in ISF adenosine. There
was a reciprocal correlation between the ISF concentration of ATP and
adenosine in preconditioned hearts. In addition, there was a significant
correlation between ISF adenosine and ATP and the inhibitory potency of
SPT [adenosine receptor antagonist 8-(p-sulfophenyl)theophylline] and
suramin [P2Y purinoceptor antagonist] or RB [reactive blue..another P2Y
purinoceptor antagonist] against functional protection conferred by IPC.
These results suggest that extracellular ATP and adenosine play a
complementary role in IPC through P2Y purinoceptors and adenosine
receptors, respectively" (2).
ATP, and its degradation products ADP, AMP and adenosine which are
released from cells in metabolic stress, form a superfamily of
signalling molecules which act upon P2X, P2Y and Pi [adenosine]
receptors. Px2 receptor activation open channels for Na+ and Ca++ and
induce short term effects, P2Y receptor activation releases Ca++ from
intracellular stores and exerts both short-term and long term effects, the
latter being potentially life-long for the genome can be altered (3).
Herein may lie the cause of the immunity apparently conferred to influenza
and even tuberculosis [consumption] by fumes to which these workers were
exposed. Preconditioning is very similar to cellular immunity and might
even have a common evolutionary origin based on a simple Wolfram rule, or
1. S. Loukogeorgakis, A. Panagiotidou, M. Broadhead, A. Donald, J.
Deanfield, R. MacAllister. Remote Ischemic Preconditioning Provides Early
and Late Protection Against Endothelial Ischemia-Reperfusion Injury in
HumansRole of the Autonomic Nervous System
Journal of the American College of Cardiology, 2005;46:450-456
2. Hideki Ninomiya, Hajime Otani, Kejie Lu, Takamichi Uchiyama,
Masakuni Kido, and Hiroji Imamura.
Complementary role of extracellular ATP and adenosine in ischemic
preconditioning in the rat heart
Am J Physiol Heart Circ Physiol 282: H1810-H1820, 2002.
3. Baljit S. Khakh and Geoffrey Burnstock. The Double Life of ATP in
Scientific American December 2009.
Competing interests: No competing interests