Question: Is it possible to reliably run a Pi in an airtight (watertight) case or is some form of ventilation required for cooling? I'm assuming it doesn't chuck out too much heat, but am wondering whether running it indefinitely this way may cause issues.

Answer: 
Yes, under usual circumstances it should be possible to run the Raspberry Pi in an airtight case. I have measured some temperatures confirming that there is amply thermal headroom.

For reference:

* 22°C room temperature
* 42°C idle

I ran [sysbench](http://sysbench.sourceforge.net/docs/#cpu_mode) to stress the CPU:

```
sysbench --test=cpu --cpu-max-prime=20000 run

```

* 45°C 20 s
* 46°C 2 m
* 47°C 5 m
* 48°C 12 m

Since the temperature did not seem to raise any further, I put a paper hood over the CPU to simulate the "airtight case scenario".

* 49°C 20 s
* 50°C 2 m

After another half an hour there was no further increase of the temperature.
According to [this test](https://www.jeffgeerling.com/blog/2019/raspberry-pi-microsd-card-performance-comparison-2019) the USB 3.0 controller on Raspberry Pi 4 cannot work at full speed if there is no fan. The slow down without a fan could be 2-3 times. In the test the maximum speed was 346 MB/s for USB 3.0 (for comparison, it was 44 MB/s for an SD card). So depending on your speed requirements and how often you need it, you may or may not need active cooling.