Now, looking at the pathophysiology of infectious exacerbations of COPD, viruses cause one-third to two-third of cases such as the ones I’ve already mentioned. Rhinovirus, the cause of the common cold, prior to COVID 19 seemed to be the most common cause of a COPD, but in those days, so is influenza, parainfluenza, the endemic coronaviruses that were circulating before COVID-19 and adenovirus. On the other hand, remember that in patients with COPD, asymptomatic was stable individuals, about 15% of them will have a positive virus, PCR tests – the viral test is helpful, but not always definitive. Bacterial infections, which we’ll focus on here, are associated with one-third to one-half of exacerbations of COPD. Many of these, especially in the West, are due to nontypeable haemophilus influenza. This means that the H.Flu type B vaccine that we use in children are not very helpful in adult patients with COPD; these are also subjected to Moraxella catarrhalis and Streptococcus pneumoniae eye infections, Pseudomonas aeruginosa and enteric gram-negative rods are seen in severe COPD around the world. In addition, they appear to be more common in Asia, for reasons that are not entirely clear. It had been speculated that it was the environment, or perhaps even the availability of common antibiotics like amoxicillin and trimethyl sulfa over the counter in some countries; but I’ll note that in the Philippines, where they do have some of these drugs available without a prescription. The predominant pathogens are Haemophilus moraxella and pneumococcus, as opposed to gram-negatives.
Now, it turns out the acquisition of a new strain of bacteria does cause an exacerbation of COPD, but a lot is this is due to the body’s inflammatory response to this new strain of organism and not so much the increased bacterial load, or frank infection. And recall also that most studies of sputum culture results are done in patients with chronic bronchitis because they’re the ones who produce the most sputum. In addition, another specific population are the COPD patients who have developed respiratory failure and require intubation in which case is a relatively straightforward way to suction deep sputum cultures. So, it’s important to understand the source of the sputum in your patient and clinical studies, as well as what the culture shows.
Now, this is an interesting slide from about 20 years ago, which again ties the FEV1 to the bacterial isolates from AECOPD. On the left hand side, you’ll see that when the FEV1 is above 50% of the predicted value, the majority of exacerbations in which isolates are obtained, are due to Streptococcus pneumonia. In addition, Haemophilus influenza and Moraxella catarrhalis are represented with some pseudomonas, probably from patients who perhaps were treated with antibiotics recently or were exposed to Pseudomonas; in the group with FEV1, that’s only 35-49% of predicted – you see, there’s some decrease in Pneumococcus and Haemophilus and a slight increase in Pseudomonas. And then the group where FEV1 is declined below one-third of the predicted value, all of the so called classic pathogens are diminished and you see a marked increase in Pseudomonas aeruginosa, which, again is in other areas, it represents not only the non-lactose fermenting Pseudomonas and Acinetobacter, but enteric gram-negatives like Klebsiella and Enterobacteria, and so forth.
Now, this is some of the data underpinning the study showing acquisition of a new bacterial strain, causing a COPD exacerbation. These authors conducted molecular typing of sputum specimens over almost five years in 81 COPD patients, and they found that – in sputum that was collected during an exacerbation, 33% or one-third, contained a new strain, whereas 15% or about one-sixth did not. And this suggests that the acquisition of a new strain of bacteria in the sputum was a trigger of COPD exacerbation. Most of these were Haemophilus, Moraxella and Pneumococcus, as we’ve mentioned, and again, this is one of the reasons that people are interested in the role of antibiotics in managing COPD exacerbations.