Dr John J. Strouse leads the discussion on pulmonary complications that can arise because of sickle cell disease.
John Strouse, MD, PhD: The most important acute pulmonary complication that we see in sickle cell disease is acute chest syndrome, which is syndromic. It can have multiple causes, but it’s defined as a new infiltrate that involves at least a lung segment and isn’t atelectasis, coupled with some symptoms of signs of acute pulmonary disease. That can be chest pain, fever, increased work of breathing, or increased respiratory rate. Some people will include cough or hypoxemia as well. Once someone has acute chest syndrome, we treat people with both specific and nonspecific treatments. Because it’s often triggered by an infection, we treat people with antibiotics, most commonly ceftriaxone and azithromycin.
Often, we want to make sure that people don’t have low oxygen and that we give people oxygen to maintain their pulse oximetry, their arterial oxygen saturation is greater than 94% or greater generally. We use incentive spirometry to keep their lungs well expanded to prevent additional atelectasis in areas of hypoxemia. If that’s not effective, or if they have worsening signs and symptoms, we’ll often transfuse them. That transfusion can interfere with the cycle of increased hypoxemia and increased acute cycling in the lung with vaso occlusion that can worsen acute chest syndrome. There are three3 common causes of acute chest syndrome in children; the most common is infection. That could be viral infections or bacterial infections of the lung. Pneumonia is the trigger for acute chest syndrome. In adults, we see more of fat embolization syndrome where people have vaso occlusion of a lung bone, and then some of the fat from the bone marrow actually embolizes to the lung and causes acute lung injury. Or we could see insight to sickling, where we get vaso occlusion of the lung, and that causes the acute chest syndrome.
Our treatment for that when it’s moderate or severe typically is transfusion. That could be simple transfusion in patients that are more anemic or in people that are sicker, or have higher hemoglobin. We’ll often do a red cell exchange, either erythrocyte or apheresis, where we use automated methods using an apheresis process, or manual exchange where we pull up blood and transfuse blood at the same time. The other common lung complication that we see is pulmonary hypertension. We can argue whether this is a lung complication or a heart complication, but it really increases pulmonary pressures.
If we screen people with echocardiography as adolescents or young adults, we’ll find increased pulmonary pressures by echocardiography in about 30% of people. When we do more specific testing like right heart catheterization, we find that many of these people do not truly have pulmonary hypertension, but they might have evidence of cardiac complications including some congestive heart failure contributing to their increased pulmonary pressures, or sometimes there are false positives. This is a common complication of sickle cell disease. We see more of it in people who have lower hemoglobin and high reticulocyte count. People who have increased hemolysis are more likely to get pulmonary hypertension. We often will treat it with disease-modifying therapies, such as hydroxyurea or regular red cell transfusion, as a way to make it more mild. We also use some of the treatments for pulmonary hypertension for it as. Our colleagues who are pulmonologists or cardiologists help with that.
We do see people with sickle cell disease having nocturnal hypoxemia. This is described both in children and adults, and it has multiple ideologies. Sometimes it’s from obstructive sleep apnea. Children with sickle cell disease often have increased tonsillar tissue, so sometimes it’s from large tonsils. We also see changes in the development of the midface. The shape of the midface bones can change some from bone marrow expansion secondary to the increased erythropoiesis that we see in people with sickle cell disease. There’s a higher incidence of obstructive sleep apnea, which can cause nocturnal hypoxemia. Nocturnal hypoxemia is concerning in people with sickle cell disease because those lower oxygen levels can lead to increased sickle cells and increased vaso occlusion. In children with sickle cell disease, it’s been associated with increased cerebral blood flow velocities and an increased risk of stroke. If there’s concerning signs or symptoms, we want to screen those people with a sleep study and treat their nocturnal hypoxemia or obstructive sleep apnea if it exists.
We also see obstructive and restrictive lung disease in people with sickle cell disease. By obstructive lung disease, we see both classic allergic asthma in children with sickle cell disease. We can see an asthma-like phenotype that’s probably related to hemolysis in people who don’t have allergic-type asthma. The prevalence of asthma in children with sickle cell disease is at least 20%, maybe higher depending on what sort of definition you use. Those children that have asthma have an increased incidence of sickle cell pain and acute chest syndrome. In adults, we see the same thing. We certainly see an increased incidence of pain events in people who have asthma. Screening people by symptoms for asthma, thinking about doing pulmonary function tests if people have respiratory symptoms, and then treating their asthma aggressively with controller medications is certainly important in the sickle cell disease.
In adults, we also see a pattern of restrictive lung disease. This is 1 of the end-organ complications of sickle cell disease. It’s more challenging to treat, but we want to try to control their sickle cell disease. We think this might be 1 of the long-term complications that we see, particularly in people who had a lot of problems with cardiopulmonary complications as children and younger adults.
Transcript edited for clarity.