Why is familial interstitial lung disease (ILD) important? How to identify cases?

In this article I will discuss about the importance of family history in the diagnosis and management of interstitial lung disease (ILD).

Most people do not know that part of my job in Manchester is to perform a clinic which is called familial interstitial pneumonia (a.k.a. the “FIP” clinic). During these consultations I collect family history information from our ILD patients and if they meet certain criteria they would then go on to have genetic testing.

I cannot put a number on the percentage of my ILD patients who have other family members with ILD or related conditions. However, I feel that whatever that number would be, it would be underestimated. The main reason is lack of time. ILD clinics, just like any other medical services, run to the limit. Being such a niche field doesn’t help, because there are few doctors with a special interest in ILD and a desire to investigate cases of parenchymal lung disease to the very end. It is time consuming work which involves a lot of administrative work, chasing different results, requesting opinions from other specialties, working as part of a team with other doctors, nurses, pharmacists etc. ILD is not for everyone.

Therefore, the few specialists in this field need to balance the lack of time with getting the best possible results for each individual patient. This usually means that we are trying to lump together similar cases in order to prescribe treatment that has a reasonable chance of working. Many ILD physicians are forced to take these decisions because the sheer amount of detective work required to make specific personalised diagnoses is unsustainable.

I introduced this preamble here because it explains why so many cases of familial interstitial lung disease are missed. Personally, I prefer the term familial interstitial lung disease as opposed to familial pulmonary fibrosis or familial interstitial pneumonia. But the name matters less, just like ILD classifications change every few years anyway. More clinicians could probably get behind a term such as familial ILD. It is less intimidating than other obscure classification terminology and may simply prompt more doctors to ask about family history. Familial ILD – family history of ILD. Ask about this! It has a certain ring to it.

Missing cases of familial ILD is, I suspect, very common. But this is not to blame only on physicians. Sometimes patients may not understand clearly what ILD is. Especially during the initial consultations for ILD, most patients are overwhelmed by the sheer amount of information that is presented to them. It’s hard for many to make the connection to other lung diseases in the family and they will not volunteer this information. The diagnosis of ILD also may have been hidden in other family members behind labels of COPD or late-onset asthma.

So how can you try to identify familial cases?

Or first, why would you?

You might find it interesting to hear that familial cases of ILD where there are telomere related gene mutations have a worse prognosis overall. You may want to follow up these patients more often. They may require earlier listing for lung transplant given their potentially faster lung function decline. If these patients are treated with high dose immunosuppression, they may actually not tolerate it well and have many adverse effects. Also, from a patient perspective you would achieve two main things: 1) give them a potential answer to the “why me?” question, and 2) help them identify family members who are dear to them who may also be at risk, to give them a potential warning. This early detection of at-risk family members may prompt early genetic testing in relatives and early screening for ILD in asymptomatic individuals. Finding ILD early gives us a bit more time to institute treatment aimed at stabilizing the condition or introducing antifibrotics as early as possible to reduce the rate of lung function decline – buy time.

I’ve answered the why, let’s now deal with the how.

The easiest thing is to just ask: Was there anyone else in your family with lung disease? Any blood relatives with lung scarring/fibrosis? Any relatives who suffered with rare or unusual diseases? Asking these questions literally takes a few seconds, but can open up a whole new avenue to explore aetiology in that patient’s case.

In our experience, if the patient answers yes to some of these questions we prefer to bring them back for a separate consultation to discuss the answers in more detail, perform a questionnaire to assess the suspicion of telomere shortening syndrome and draw a family tree to better understand how the ILD and related conditions are transmitted over the generations. It is fascinating what stories we hear during these consultations – stories which only make us want to ask more and more. It truly gives a glimpse into the complexities of the human species.

To go into a bit more detail, I briefly mentioned the questionnaire that we go through. This is very simple. We ask whether the patient or their close blood relatives have had:

1. Onset of ILD/pulmonary fibrosis before the age of 60
2. Family history of ILD
3. Personal or family history of hematological disease (malignancy, anemia)
4. Personal or family history of autoimmune disease/autoimmune features
5. Frequent cancers in the family
6. Early grey hair (<25)
7. Early menopause (<45)
8. Family history of 2 specific conditions associated with telomere shortening – aplastic anemia or diskerarosis congenita.

Answering yes to several of these makes it relatively easy to realize that there is something going on in the family, with a high possibility of disease inheritance.

The next step is to actually draw a family tree, preferably done face-to-face, together with the patient guiding us. We specifically ask about:

1. Children
2. Partner
3. Siblings
4. Parents
5. Paternal and maternal siblings (uncles and aunts)
6. Grandparents

If we ask systematically about all of them, it makes it easier not to miss important conditions. Often enough, going through the levels of the family in this way jolts the memory and patients remember more. They may volunteer information about nieces and nephews etc.

As you can probably appreciate, this takes time, hence why taking family history is usually done in a separate appointment. We generally reserve one hour for these sessions, which also allows time to consent for potentially performing genetic testing and filling in the required forms for this.

If positive results are found for genetic mutations, patients are then referred for genetic counselling in order to identify family members at risk of developing ILD or related conditions.

I believe that by taking the extra time to actually look at family history in detail we are driving the field of ILD forward. We are uncovering that more people than previously appreciated have familial ILD. We also set the scene for rapid screening and intervention. The current ILD treatments are best given early, therefore creating a rapid circuit to identify family members at risk through careful history taking may save lives.