1- Do you have any impact on the source code for publishing to iOS? 
If you use a ANE that is target only for Android => Yes.
You have to proper configure application descriptor.

2- Do I need a Macbook to create or publish my application? 
Typically yes but I read about a way to do that on a windows machine.
I will need to create a assets car icon file and that requires a macOS
however there is free online services do that for you.

3- Will I be able to create my application without problems in Apache Flex 
version 4.16.1? 
I'm using Apache Flex (since Adobe Flex) for both Windows, macOS, Android
and iOS without issues however that was the past and the present.
I don't know about the future.
I don't really believe in issues with Flex on a near future.
The issue is about AIR, if there is a change on the Apple Store that AIR
could not follow but that danger is present on every runtime.
The only option bullet prof is to go for native development.

4 - Do you have to pay and do I have setup issues ?
Yes, yes and yes.
You have to pay a annually fee.
You have to configure a lot of things (a macOS it's highly recommended).



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