Vital capacity

Now, uh, in terms of breathing, this was, uh, most interesting to me, this aspect.

So, uh, we look at, uh, a number of breathing markers, but the two most important are the FEV1, so the forced expiratory volume and, um, and, uh, in the first second, and FVC, which is forced vital capacity.

And, and both of these improved by fourteen and twelve percent respectively.

And again, the FVC in ALS is supposed to decline, uh, on this sort of trend.

So if you look at it, it...

the orange bars show what should have happened in someone with ALS and, and this guy stayed the same or even improved.

Let's look at the mechanical capacity of your lungs first.

A recent trial measured forced vital capacity, or FVC.

Okay, an FVC is basically the total volume of air you can violently blow out after taking the deepest breath possible, correct?

Yes.

It is the absolute gold standard benchmark pulmonologists use to evaluate your lung function.

In a healthy adult, your FVC is a stubborn fixed number.

It's based on your height, your age, and your rib cage size.

So it shouldn't really change on a day-to-day basis.

They look at your sex.

And then they look at your score on the FEV1 and the FVC.

So basically, they're looking at lung content.

And at another level, they're looking at your exhalation velocity, which is basically how strong your lungs are with the ability to to exhale the air that's in your lungs.

36% of participants currently smoked and 31% previously smoked.

There were no statistically significant associations of HIV with FEV1 or FVC, but there was an association with lower diffusing capacity.

Significant differences in lung function were noted by menopausal phase in women who were 41 to 50 years of age, but not in those who were 51 to 60 years of age.

Among those 41 to 50, women in late perimenopause had reductions of 109 mLs in FEV1 and 125 mLs in FVC, and postmenopausal women had reductions of 310 mLs in FEV1 and 307 in FVC.

Late perimenopausal women had a negative 1.4 mL per minute per mmHg lower diffusing capacity.

These results show that menopausal phase is associated with lung function in women with HIV and women without HIV.

well.

The other piece I like to throw in there is that COPD is a disease of the aging lung and And these days, when we start indexing to Z-score that is age-adjusted, people can end up having dyspnea, but their spirometry is not as abnormal as it used to be if we were looking at it in a more traditional FEB1-FVC perspective.

And as you develop airspace enlargement with emphysema and the CDC's data where they went and knocked on doors just suggested that a large number of elderly actually have COPD, but don't complain of their lungs.

So there's a large burden of elderly.

You don't have to see obstruction to give an inhaler and wonder if episodic obstruction is in the background in the mix.

But COPD is fixed obstruction.

You're going to see obstruction, and you want to make sure that your FEV1-FVC ratio is abnormal.

either by Z-score or the fixed ratio of 0.7. And what you do beyond that will sometimes subtly help the endotypes, the subphenotypes, after the diagnosis about how much is emphysema, how much is chronic bronchitis, or this whole mix of having an asthmatic component in there as well.

Exactly.

You’re constantly monitoring the forced vital capacity, the FVC, because if the diaphragm weakens and that FVC drops, the patient is silently losing the mechanical ability to pull oxygen into their lungs.

It’s terrifying.

It really is.

One more thing here.

They did also try to adjust for FEV1 over FVC, which is a lung function.

And there was no basically association or quantification over that.

And we do have this share here where we can share this.

Uh, this study was a multicenter, phase two, double-blind, randomized control trial of IV allogenic bone marrow-derived mesenchymal stromal cells in lung transplant recipients with new-onset CLAD.

Eligible recipients were adults who had undergone bilateral or single lung transplantation more than six months before screening and had developed new-onset CLAD, defined as a persistent fall of greater than twenty percent in FEV1 and/or FVC from best post-transplant values within twelve months before screening.

Participants were randomized one to one to receive mesenchymal stromal cells twice weekly, uh, uh, for two weeks or placebo.

Key exclusion criteria included active infection, acute rejection within the prior three months, commencement of azithromycin, extr-extracorporeal photopheresis, total lymphoid irradiation, or fundoplication all within eight weeks of the screening visit, and malignancy within five years, with the exception of adequately treated non-melanoma skin cancer.

Again, not had any issue with his respiratory muscles yet or his swallow, but was quite worried.

So we, and with the slightly reduced reflexes, they did have the back of the mind, is this an odd Guillain-Barré variant that could be happening? So we got them into HDU.

that afternoon, just because I think if it was somewhere else other than the satellite surgical ward, they could have done some of these things, but I think as soon as we heard about the idea that you were doing FVCs and things, they thought, no, and let's bring them to somewhere where we can have just closer monitoring.

Plus, the fact that things were changing so quickly, we don't want to be in an instance where we're scrambling.

And in that instance, they also organised a...